JPH0138087B2 - - Google Patents
Info
- Publication number
- JPH0138087B2 JPH0138087B2 JP54049831A JP4983179A JPH0138087B2 JP H0138087 B2 JPH0138087 B2 JP H0138087B2 JP 54049831 A JP54049831 A JP 54049831A JP 4983179 A JP4983179 A JP 4983179A JP H0138087 B2 JPH0138087 B2 JP H0138087B2
- Authority
- JP
- Japan
- Prior art keywords
- tyrosine
- amount
- brain
- norepinephrine
- blood pressure
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 230000036772 blood pressure Effects 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 25
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 20
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 18
- 239000002220 antihypertensive agent Substances 0.000 claims description 6
- 230000037396 body weight Effects 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 claims description 4
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 claims description 4
- CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 claims description 4
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 claims description 4
- CJCOBMTYEDBBSY-UHFFFAOYSA-N 2-phenoxybenzamide Chemical compound NC(=O)C1=CC=CC=C1OC1=CC=CC=C1 CJCOBMTYEDBBSY-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229960003883 furosemide Drugs 0.000 claims description 2
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 claims description 2
- 229960003602 guanethidine Drugs 0.000 claims description 2
- 229960002474 hydralazine Drugs 0.000 claims description 2
- 229960003712 propranolol Drugs 0.000 claims description 2
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 claims description 2
- 229960002256 spironolactone Drugs 0.000 claims description 2
- 239000003451 thiazide diuretic agent Substances 0.000 claims description 2
- 229940121792 Thiazide diuretic Drugs 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 86
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 85
- 210000004556 brain Anatomy 0.000 description 69
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 44
- 229940024606 amino acid Drugs 0.000 description 35
- 150000001413 amino acids Chemical class 0.000 description 34
- 229960002748 norepinephrine Drugs 0.000 description 34
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 34
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 33
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 31
- 241000700159 Rattus Species 0.000 description 22
- 229960003638 dopamine Drugs 0.000 description 22
- 230000000694 effects Effects 0.000 description 17
- 229960004799 tryptophan Drugs 0.000 description 17
- 229940076279 serotonin Drugs 0.000 description 16
- 210000000225 synapse Anatomy 0.000 description 16
- 239000003814 drug Substances 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 229940079593 drug Drugs 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 210000002569 neuron Anatomy 0.000 description 12
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 11
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 11
- 229960003081 probenecid Drugs 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 230000007423 decrease Effects 0.000 description 9
- 206010020772 Hypertension Diseases 0.000 description 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 8
- 238000009825 accumulation Methods 0.000 description 8
- 230000007935 neutral effect Effects 0.000 description 8
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 230000037213 diet Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 239000005018 casein Substances 0.000 description 6
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 6
- 235000021240 caseins Nutrition 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000004474 valine Substances 0.000 description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 102000003946 Prolactin Human genes 0.000 description 4
- 108010057464 Prolactin Proteins 0.000 description 4
- 108091000117 Tyrosine 3-Monooxygenase Proteins 0.000 description 4
- 102000048218 Tyrosine 3-monooxygenases Human genes 0.000 description 4
- 229940030600 antihypertensive agent Drugs 0.000 description 4
- 235000015115 caffÚ latte Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- 229940097325 prolactin Drugs 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000007306 turnover Effects 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 150000002871 norepinephrines Chemical class 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 2
- -1 3,4,5-trimethoxybenzoyl Chemical group 0.000 description 2
- FBWPWWWZWKPJFL-UHFFFAOYSA-N 3-Methoxy-4-hydroxyphenylethyleneglycol Chemical class COC1=CC(C(O)CO)=CC=C1O FBWPWWWZWKPJFL-UHFFFAOYSA-N 0.000 description 2
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 2
- 229940000681 5-hydroxytryptophan Drugs 0.000 description 2
- 108060003345 Adrenergic Receptor Proteins 0.000 description 2
- 102000017910 Adrenergic receptor Human genes 0.000 description 2
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
- 102000015554 Dopamine receptor Human genes 0.000 description 2
- 108050004812 Dopamine receptor Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004531 blood pressure lowering effect Effects 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 229960002896 clonidine Drugs 0.000 description 2
- 229960002925 clonidine hydrochloride Drugs 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 229960002003 hydrochlorothiazide Drugs 0.000 description 2
- 230000001077 hypotensive effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000000691 measurement method Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- WZHJKEUHNJHDLS-QTGUNEKASA-N metergoline Chemical compound C([C@H]1CN([C@H]2[C@@H](C=3C=CC=C4N(C)C=C(C=34)C2)C1)C)NC(=O)OCC1=CC=CC=C1 WZHJKEUHNJHDLS-QTGUNEKASA-N 0.000 description 2
- 229960004650 metergoline Drugs 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- GEFQWZLICWMTKF-CDUCUWFYSA-N (-)-alpha-Methylnoradrenaline Chemical compound C[C@H](N)[C@H](O)C1=CC=C(O)C(O)=C1 GEFQWZLICWMTKF-CDUCUWFYSA-N 0.000 description 1
- RQPKNXVVIBYOBX-KDBLBPRBSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-2-(dihydroxyamino)-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.ON(O)[C@H](C(O)=O)CC1=CC=CC=C1 RQPKNXVVIBYOBX-KDBLBPRBSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- WUFPNASKMLJSND-UHFFFAOYSA-N 3-methoxy-4-hydroxyphenylethyleneglycol sulfate Chemical compound COC1=CC(C(O)CO)=CC=C1OS(O)(=O)=O WUFPNASKMLJSND-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000027219 Deficiency disease Diseases 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical class O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex⢠Substances 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000004716 alpha keto acids Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229940082992 antihypertensives mao inhibitors Drugs 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical compound CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 229960004205 carbidopa Drugs 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000002925 chemical effect Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000003954 decarboxylase inhibitor Substances 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 238000004141 dimensional analysis Methods 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 231100000673 doseâresponse relationship Toxicity 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 239000003777 experimental drug Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 235000008085 high protein diet Nutrition 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229940121356 serotonin receptor antagonist Drugs 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Description
æ¬çºæã¯äººäœãåç©ã®è¡å§éäžå€çµæç©ã«é¢ã
ããã®ã§ããã äžå±€è©³çŽ°ã«ããã°æ¬çºæã¯ãç¥çµã·ããã¹äžã®
ãããã³ããã³ãã«ãšããããªã³ã®éã調ç¯ïŒå¢
å ãŸãã¯æžå°ïŒããããšã«ãã人äœãåç©ã®è¡å§
éäžå€çµæç©ã«é¢ãããã®ã§ããã ç¥çµäŒéç©è³ªã§ãããããã³ããã³ãã«ãšãã
ããªã³ããžããããã·ããšãã«ã¢ã©ãã³ïŒããïŒ
ããèªå°ãããç©è³ªã§ããããšã¯æ¢ã«å ¬ç¥ã§ã
ããäžæ¹ããã¯ãã¢ããé žã§ããããã·ã³ã®é µçŽ
åŠçããããã·ã«åã«ãããã€ãã³äžã§çæãã
ãã®ã§ããããã®ããã»ã¹ã¯ãé µçŽ ã§ããããã·
ã³ããããã·ã©ãŒãŒã®è§Šåªäœçšã®ããšã§é²è¡ã
ããããã¯ãé µçŽ ã§ããâã¢ããé žãã«ã«ãã
ã·ã©ãŒãŒïŒAAADïŒã«ããè±ã«ã«ããã·ã«åã
ããŠãããã³ã«ãªãããã«ãšããããªã³ã¯ãé µçŽ
ã§ãããããã³âβâããããã·ã©ãŒãŒããå«ã
ãã€ãã³äžã§ãããã³ããçããããã®äžé£ã®å
å¿ã«ãããŠãåŸé段éã¯ããã·ã³ãããããžã®å€
æ段éã§ããããã®çç±ã®ããã«ãããŒãã³ãœã³
ç ã®åŠããããã³æ¬ ä¹æ§çŸç ã«èµ·å³ãã身äœé害
éšãæããæ£è ã«ãããã³æäžãè¡ãªãããããš
ããã€ããããããªããéœåã®æªãããšã«ã¯ãã
ããæäžãããšããã¯èº«äœå šäœã®çŽ°èã«åžåãã
ãŠãããã³ã«å€ãããããã«ãã€ãŠããããã®çŽ°
èã«ãããæ£åžžãªä»£è¬ããã»ã¹ã劚害ããããšã
ãäžéœåãªäºæ ãçããã®ã§ãããããã«ãã
ã¯ãç¥çµäŒéç©è³ªã§ããã»ãããã³ã®æ£åžžãªäººäœ
å èç©ã劚害ãããã€ãâã¢ããã·ã«ã¡ããªã
ã³ååç©ã®è³å ååšéãäœäžãããããããã®äž
ææã®å¯äœçšã®ããã«æ£è ã«ããããããªã³âãª
ãçŸè±¡ãçãèªããããããšãããããããŠæå Ž
åã«ã¯ç²Ÿç¥ç ç城åãèªããããããšããããåŸ
ããã·ããã¹äžã®ãããã³ããã³ãã«ãšããããª
ã³ã®éãå¢å ãããäœçšãæããä»çš®è¬å€ã®äŸã«
ã¯ã¢ãã¢ãã³ãªãã·ããŒãŒæå¶å€ïŒããã¯åèšã®
ç¥çµäŒéç©è³ªã®å解ãé 延ããããã®ã§ããïŒã
ãã³ïŒæ žåã®ææãã€å€ïŒã¢ã³ãããã¬ãµã³ãïŒ
ããããããããããã®ååç©ã¯æå§çç¶ã䌎ã
çŸç ã®æ²»çå€ãšããŠäœ¿çšãããŠãããããããã
ãŸããã·ããã¹äžã®ãããã³ããã³ãã«ãšããã
ãªã³ã®éã®å¢å äœçšã®ä»ã«æ¯èŒçéç¹ç°æ§ã®ååŠ
çäœçšãæãããã®ã§ãã€ãŠãããªãã¡çš®ã ã®å¯
äœçšãæããããšãã°è¡å§äžæäœçšçãæããã
ããããŠãã®è¡å§äžæã¯ãã¢ãã¢ãã³ãªãã·ããŒ
ãŒæå¶å€ãæäžããæ£è ãæçš®ã®é£åãé£ã¹ããš
ãçã«èµ·ããã®ã§ããã ãã¹ãâã·ããããã¯ãããã³âããã³ãã«ãš
ããããªã³âã¬ã»ãã¿ãŒãçŽæ¥ã«æŽ»æ§åãããè¬
å€ãæäžããããšã«ããããããããŒãžãã¯
ïŒdopaminergicïŒâããã³ãã«ã¢ãã¬ããŒãžãã¯
ã·ããã¹ãééããä¿¡å·ã®äŒéæ§ãé«ããããšã
ã§ããããã®ãããªè¬å€ã®äŸã«ã¯æ¬¡ã®ãã®ããã
ãããïŒã¢ãã¢ã«ãããããã¢ã¯ãªããã³ïŒãã
ãã³ãªã»ãã¿ãŒïŒãã¯ãããžã³ãαâã¡ãã«ãã
ïŒåååãã¢ã«ãã¡ãããââããã¯è³å ã§Î±âã¡
ãã«ãã«ãšããããªã³ã«å€æãããïŒïŒãã«ãšã
ãããªã³ã¬ã»ãã¿ãŒïŒããããã®ååç©ã¯æ¢è¿°ã®
ä»çš®è¬å€ãšåæ§ã«ãè³ããã³ä»ã®äœå çµæå šäœã«
ãããŠå¯Ÿå¿ã¬ã»ãã¿ãŒäžã§äœçšãããã®ããã«äž
ææã®å¯äœçšã瀺ããã®ã§ããã ã·ããã¹äžã«ãããã³ãŸãã¯ãã«ãšããããªã³
ãéå°éååšãããšãã«èµ·ãä»çš®çŸç ã®äŸã«ã¯æ¬¡
ã®ãã®ããããããïŒç²Ÿç¥ç ïŒãããã³ã®éã極
端ã«å€ãïŒãéåé害çïŒmovement disordersïŒ
ããšãã°ã¿ãŒãžãã»ãžã¹ããã·ã¢çããã³ã®ã¬
ã¹ãããã©ãããŠã¬ããçå矀ïŒãããã³ã®éã
極端ã«å€ãïŒïŒé«è¡å§ããã³äžæŽèïŒäº€æç¥çµã
ã€ãã³ããæŸåºããããã«ãšããããªã³ã®éã極
端ã«å€ãïŒãçŸåšãããã®ç æ°ã®æ²»çã¯äžè¬ã«ã
ãããã³ãŸãã¯ãã«ãšããããªã³ãšãã®åŸæã¬ã»
ãã¿ãŒïŒportâreceptorsïŒãšã®ã€ã³ã¿ãŒã©ã¯ã·
ãšã³ã劚害ããè¬å€ïŒããšãã°ããšããã¢ãžã³ãŸ
ãã¯ãããããšãã³ïŒãçšããŠè¡ãªãããŠããã
ããããªãããããã®è¬å€ã¯ãã¹ãŠãè¥å¹²ã®éç¹
ç°æ§äœçšãè¡šãããã®ã§ãã€ãŠããããã€ãŠãã®
æçšæã«å¯äœçšãè¡šãããããšãããã ç¥çµäžã®ããã·ã³ã®éãå€ããããšã«ãããã
ãã³ãŸãã¯ãã«ãšããããªã³ã®éãå¢å ãŸãã¯æž
å°ãããè©Šã¿ã以åã«è¡ãªããããããã®è©Šã¿ã¯
æåããªãã€ãããªããªãã°è³ããã³çš®ã ã®çµæ
ã®äžã®ãããã®ååç©ã®éãå€åãããããšã¯è¡
ãããªãã€ãããã§ãããè³å ã®ããã®æ¿åºŠã¯ã
æå®ã®å®éšæ¡ä»¶äžã§ã¯ãããã³ããã³ãã«ãšãã
ããªã³ã®åæé床ã«æ¯äŸããŠå€åãããããŠè³å
ã®ããã®æ¿åºŠã¯ãè³å ã®ããã·ã³ã®æ¿åºŠã®å¢å ã«
ããå¢å ãããããšãã§ãããã€ãè³å ã®ããã®
æ¿åºŠã¯ãè³å ã®ããã·ã³ã®æ¿åºŠãäœäžããããã
ãªåŠçã«ãã€ãŠäœäžãããããšãã§ããïŒã©ãã
ãçšããå®éšïŒããšãæåã«èŠåºããç 究è ã¯ã¯
ãŒããã³ã§ãããããµã€ãšã³ã¹ã第185å·»183é â
第184é ïŒ1974幎ïŒæ12æ¥ïŒããè³å ã®ããã·ã³ã®
éãå¢å ãããçºã®åŠçæ¹æ³ã®ïŒã€ã¯ãããã·ã³
ããèªäœãæäžããããšã§ãã€ããè³å ã®ããã·
ã³ã®éãæžå°ãããçºã®åŠçæ¹æ³ã®ïŒã€ã¯ãè¡æŒ¿
äžã®ããã·ã³ïŒãã©ãºãããã·ã³ïŒã®è³å 移è¡æ§
ãšç«¶åããæ§è³ªãæããä»çš®äžæ§ã¢ããé žã®ãã¡
ã®ïŒã€ïŒäŸãã°ãã€ã·ã³ïŒãæäžããããšã§ã
ãããã®åŠèª¬ãçºè¡šããã以åã«ã¯ãåèšã®åŸé
段éã®åå¿ãé²è¡ãããé µçŽ ã§ããããã·ã³ãã
ããã·ã©ãŒãŒã¯ããã·ã³ã«ããé«åºŠé£œåç¶æ ã«ãª
ã€ãŠããã®ã§ãè³å ã®ããã·ã³ã®éã®å¢å ãŸãã¯
æžå°ãããã·ã³ãããããžã®å€æåå¿ã«åœ±é¿ãäž
ããããšã¯ãªãã§ããããšæãããŠããã®ã§ã
ããäžæ¹äžèšã®ã¯ãŒããã³çã®è«æãŸãã¯å ¶åŸã«
çºè¡šãããã®ããœã³åã³ã¯ãŒããã³ã®è«æ
ããBiochem.Pharmacologyã第26巻第1137é â
第1142é ïŒ1977幎ïŒæå·ïŒã«ã¯ãããèç©éã«é¢
ããåèšã®å€åã¯ãè³å ã®ãããã³ãŸãã¯ãã«ãš
ããããªã³ã®éã®å€åã䌎ããã®ã§ããããšã¯å š
ãé瀺ãããŠããªãããŸããè³å ã®ããã·ã³ã®é
ãå€ããããšã«ãããã·ããã¹ãžã®ãããã³ãŸã
ã¯ãã«ãšããããªã³ã®æŸåºéã«åœ±é¿ãäžããããš
ãã§ããããšããäžèšã®æç®ã«ã¯å šãé瀺ãããŠ
ããªãã ã·ããã¹äžã«å®éã«ååšãããããã³ããã³ïŒ
ãŸãã¯ãã«ãšããããªã³ã®éãå¢å ãŸãã¯æžå°ã
ããæ段ãéçºããããšã¯ãéåžžã«å¥œãŸããããš
ã§ããããã€ãã³äžã«è²¯èµãããååŠäŒéç©è³ª
ïŒããªãã¡ã·ããã¹äŒéç©è³ªïŒã®ãã¹ãŠã®ååã
çããã·ããã¹ã«å®¹æã«æŸåºã§ãããã®ãšã¯éã
ãªããšããããšãçŸåšå ¬ç¥ã§ãããããã·ããã¹
äžã§ã®è©²ååŠäŒéç©è³ªã®éçå€åã«äŒŽã€ãŠãè³ãŸ
ãã¯ä»ã®çµç¹ã®äžã®ãããã³ãŸãã¯ãã«ãšããã
ãªã³ã®å šéãå€åãããšã¯éããªããåèšã®ã
ããMAOæå¶å€ãããšããã¢ãžã³ããã³ä»ã®è¬
å€ã®æäžæã«äŒŽããããªäžææã®å¯äœçšããªãã
ãã€çååŠçç¹ç°æ§ãæãããããªæ段ãéçºã
ãã®ãæãŸããã®ã§ããããã®ãããªæ段ã¯ãã
ãèªäœãç æ°ã®ããã®æçšãªæ²»çæ段ãšããŠå©çš
ã§ããã§ãããããããã¯ãçš®ã ã®è¬å€ã®æ²»çå¹
æãäžå±€é«ããããã«ãåèšã®æ段ã¯è©²è¬å€ãšçµ
åãããŠå©çšã§ããã§ãããã çŸåšãè¡å§éäžå€ãšããŠæãåºã䜿çšãããŠã
ãå»è¬åã®ãã¡è¥å¹²ã®ãã®ãããšãã°ãαâã¡ã
ã«ããïŒã¢ã«ãã¡ããïŒã11ïŒ17αâãžã¡ããã·
â18βâãïŒïŒïŒïŒïŒïŒâããªã¡ããã·ãã³ãŸã€
ã«ïŒãªãã·ã3βïŒ20αâãšãã³ãã³â16βâã«ã«
ãã³é žã¡ãã«ãšã¹ãã«ïŒã¬ã»ã«ãã³ïŒãïŒâïŒïŒïŒ
ïŒâãžã¯ããããšãã«ã¢ããïŒâïŒâã€ãããŸãª
ã³ãã€ããã¯ãã©ã€ãïŒã¯ãããžã³ãã€ããã¯ã
ã©ã€ãïŒçã¯ã人äœå ã§ããã©ã¯ãã³ã®åæ³ãåº
æãããã®ã§ããããã®å¯äœçšã¯å¥œãŸãããªãã
ã®ã§ããããªããªãã°ãããã©ã¯ãã³ã®åŸªç°éã®
å¢å€§ã¯æçš®ã®èºã¬ã³ã®æ¡å€§ãä¿é²ãããã€ç·æ§ã«
ã¯é°èã®åå ãšãªãåŸãããšãæè¿å ±åãããã
ãã§ããããããã€ãŠãçŸåšã®æ²»çæ³ã®ä»£ãã«å©
çšã§ãããããã¯çŸåšã®æ²»çæ³ã®è£åæ²»çæ³ãšã
ãŠå©çšã§ãããã€ããã©ã¯ãã³ã®åæ³ãä¿é²ããª
ããããªé«è¡å§éäžæ²»çæ³ãéçºããããšãéåžž
ã«æãŸããã®ã§ããã æ¬çºæã¯äžæ¢ç¥çµç³»ã®ã·ããã¹äžã®ãã«ãšãã
ããªã³ã®éïŒçžå¯ŸéïŒã®äœäžã«äŒŽãé«è¡å§çã®ã
ãã®è¡å§éäžå€çµæç©ãæäŸãããã®ã§ãããç¥
çµäžã®ããã·ã³ã®éãå¢å ãŸãã¯æžå°ããããã
ãªåŠçã¯ãã·ããã¹äžã®ãããã³ãŸãã¯ãã«ãšã
ãããªã³ã®æŸåºéã®å¢å ãŸãã¯æžå°ãããããã
ã®ã§ãããããããŠåŸè ã®å Žåã®å¢å éãŸãã¯æž
å°éã¯ãããããåè ã®å Žåã®å¢å éãŸãã¯æžå°
éã«å¯Ÿå¿ããå€ã§ããããšãæ¬çºæè ãæ€åºŠèŠåº
ãããã®çºèŠã«åºããŠæ¬çºæãå®æãããã®ã§ã
ããããã·ã³ããã®ãã¬ã«ãŒãµãŒïŒåé§äœïŒããš
ãã°ããšãã«ã¢ã©ãã³ãŸãã¯ä»ã®äžæ§ã¢ããé žã¯
åç¬ãŸãã¯æ··åç©ã®åœ¢ã§ããã€ä»ã®è¬å€ãšäžç·
ã«ããŸãã¯äžç·ã«ããã«æäžã§ããããã«ãã€
ãŠãè³å ã®ããã·ã³ïŒããã³ããšãã«ã¢ã©ãã³ïŒ
ã®éãå¢å ãŸãã¯æžå°ãããããšãã§ããããã
ãã®æäžã«ãã€ãŠãäžæ¢ç¥çµç³»ã®ã·ããã¹äžã®ã
ã«ãšããããªã³ã®äžè¶³ã«èµ·å ããé«è¡å§çãæ²»ç
ã§ãããåæ§ã«ãåèšæ··åç©äžã®ããªãããã¢ã³
ãŸãã¯ä»ã®ã¢ããé žã®ååšå²åãçš®ã å€ããããš
ã«ããããããã¯ããªãããã¢ã³ãä»ã®ã¢ããé ž
ãšäžç·ã«ããã«æäžããããšã«ããè³å ã®ã»ãã
ãã³ãŸãã¯ä»ã®ç¥åŸäŒéç©è³ªã®åæéããã³ã·ã
ãã¹ãžã®ãã®æŸåºéã調ç¯ã§ãããã»ãããã³å
æéã®å¢å ã«ããè¡å§ãäœäžãããããšãå¯èœã§
ãããã»ãããã³åæéãå¢å ãããããã«ããª
ãããã¢ã³ã䜿çšããããšã¯ãå¥ã®ã¢ããé žã§ã
ãïŒâããããã·ããªãããã¢ã³ïŒããã¯é£ç©äž
ã«ååšããããã€éåžžã¯äººäœå ã§æ¶è²»ãããªãã
ã®ã§ããïŒã䜿çšããããšãããäžå±€å¥œãŸããã
ãšã§ããããªããªãã°ããªãããã¢ã³ã¯ãã€ãã³
äžã§ã»ãããã³ã«å€æãããããããŠãã®ãã€ã
ã³ã¯éåžžã»ãããã³ïŒããã¯äŒéç©è³ªã®ïŒçš®ã§ã
ãïŒãåæãããšããã§ãããäžæ¹ãïŒâããã
ãã·ããªãããã¢ã³ã¯çš®ã ã®åã®çŽ°èã®äžã§éç¹
ç°çã«ã»ãããã³ã«å€æããåŸããã®ã§ãã€ãŠã
ãã®ããã«çš®ã ã®å¯äœçšãçããããšãããåŸã
ããã§ããããã«ãšããããªã³æŸåºæ§ã®ãã€ãã³
ãç¹ã«é«æŽ»æ§ã®ãã®ãåŠããšããããšã¯ç¡é¢ä¿ã«
ããã·ã³ã®æäžã«ããã·ããã¹äžã®ãã«ãšããã
ãªã³ã®éãå¢å ãããããšãã§ãããè³å ã®ããª
ãããã¢ã³ã®éãæžå°ãŸãã¯å¢å ãããããšã«ã
ããã»ãããã³æŸåºéãæžå°ãŸãã¯å¢å ãããã
ãšãã§ãããæå®ã®äžæ§ã¢ããé žæ··åç©ã®äžã®ã
ãã·ã³ã®ååšæ¯çã調æŽããããšã«ããããã«ãš
ããããªã³ã®æŸåºéãå¢å ãŸãã¯æžå°ãããããš
ãã§ãããå°éæäžã®å Žåã«ã¯ãããã·ã³ã®ä»£ã
ã«ããšãã«ã¢ã©ãã³ã䜿çšããããšãã§ãããåŸ
èšã®åŠãããã«ãšããããªã³ã®æŸåºéã調ç¯ããª
ããã·ããã¹ãžã®ã»ãããã³ã®æŸåºéã調ç¯ãã
ããã«ãåèšäžæ§ã¢ããé žæ··åç©äžã«ååšãã
ãããªãããã¢ã³ã®éšåããå©çšããããšãã§ã
ãããããã®ã¢ããé žã¯ãéé¢ã¢ããé žãå¡©ããš
ã¹ãã«ãããããã®åœ¢ã§æäžã§ãããŸãã¯äœå ã§
ã¢ããé žã«å€æãããååç©ïŒããšãã°Î±âã±ã
é žïŒã®åœ¢ã§æäžã§ãããããŠãã®æäžã¯ãè ¹èå
æäžãç®äžæäžãçèå æäžãŸãã¯çµå£æäžã®åœ¢
ã§è¡ãããšãã§ããã æ¬çºæã«åŸãã°ãããã·ã³ããã³ïŒãŸãã¯ãã
ã·ã³ãã¬ã«ãŒãµãŒïŒããšãã°ããšãã«ã¢ã©ãã³ïŒ
ããã³ïŒãŸãã¯ä»ã®äžæ§ã¢ããé žãåç¬ã§ããŸã
ã¯ïŒçš®ãŸãã¯ãã以äžã®å ¬ç¥è¡å§éäžè¬å€ãšçµå
ããŠæ£è ã«æäžãããããã«ãã€ãŠãã·ããã¹ãž
ã®ãã«ãšããããªã³ã®æŸåºéãå¢å ãããããšã
ã§ãããåæã«ãããªãããã¢ã³ã®åç¬æäžã«ã
ãããããã¯ã¢ããé žæ··åç©äžã®ããªãããã¢ã³
ã®ååšæ¯çãçš®ã å€ããããšã«ãããã»ãããã³
ã®æŸåºéãå¶åŸ¡ã§ããããã«ãšããããªã³æŸåºæ§
ãã€ãã³ãŸãã¯ã»ãããã³æŸåºæ§ãã€ãã³ãç¹ã«
é«æŽ»æ§ã®ãã®ã§ãããåŠããšããããšã¯ç¡é¢ä¿
ã«ãã¢ããé žæ··åç©ã䜿çšããããšã«ãããã·ã
ãã¹ãžã®ãã«ãšããããªã³ãŸãã¯ã»ãããã³ã®æŸ
åºéãçš®ã å€ããããšãã§ãããåæ§ã«ãããã·
ã³ãŸãã¯ããªãããã¢ã³ã®è³å 移è¡æ§ïŒç§»è¡éïŒ
ãšç«¶åãåŸã移è¡æ§ãæããã¢ããé žæ··åç©ãæ
äžããŠè³å ã®ããã·ã³ãŸãã¯ããªãããã¢ã³ã®é
ãæžå°ãããããšã«ããããã«ãšããããªã³ãŸã
ã¯ã»ãããã³ã®æŸåºéãæžå°ã§ããããã«ãã€
ãŠãããšãã°äžæ¢ç¥çµç³»ã«èµ·å ããäœè¡å§çã«æ©
ãæ£è ãæ²»çã§ããã ããã·ã³ã®è¡å§éäžäœçšã®æ£ç¢ºãªã¡ã«ããºã ã¯
æªã å€ã€ãŠããªãããã©ããçäœãžã®ããã·ã³ã®
å šäœçšã¯ãã¢ã«ãã¡ãããã¯ãããžã³ãã€ããã¯
ãã©ã€ããŸãã¯ã¬ã»ã«ãã³ã®äœçšãšã¯çžç°ãªãã
ã®ã§ãããšæãããããªããªãã°ããã·ã³ã¯ãã
ã©ã¯ãã³ã®åæ³ãå¢å ãããªãããã§ããã æ¬çºæã®çµæç©ã¯çµå£æäžãè ¹èå æäžãç®äž
æäžãéèå æäžãŸãã¯çèå æäžã«ããæäžã§
ããããã®ã¢ããé žã¯ãã®ãŸãŸã®åœ¢ã§äœ¿çšã§ãã
ãããã¯å¡©ãŸãã¯ãšã¹ãã«ãŸãã¯ããããã®åœ¢ã§
䜿çšã§ãããããã¯ãçäœå ã§ã®ä»£è¬äœçšã«ãã
ã¢ããé žã«å€æã§ããååç©ïŒããšãã°Î±âã±ã
ã¢ããé žïŒã®åœ¢ã§äœ¿çšã§ãããããã¯ãã€ã³ã·ãŠ
ãªã³ã»ãããã³ãèªãåºãããšã«ããè³å åžåæ§
ãå€ããããšãã§ãããããªçæ°Žåç©ãšäžç·ã«ã
ãŸãã¯äžç·ã«ããã«æäžã§ããããã®çµæç©ã¯æ°Ž
ãŸãã¯æžèé£å¡©æº¶æ¶²ã®åŠãä»»æã®ç¡å®³ããã¯ã«ã«
溶解ãŸãã¯æ··åããŠäœ¿çšãããããŸãã¯åžžçšåºäœ
åžéå€ãŸãã¯æ äœãå«ãé å€ãŸãã¯ç²å€ã®åœ¢ã§äœ¿
çšããã®ã䟿å©ã§ãããè¡å§éäžå€ãšããŠäœ¿çšã
ãå Žåã«ã¯ããã®çµæç©ã¯ãäžææã®å¯äœçšãé²
æ¢ã§ãããããªæ¿åºŠã§æäžããã®ã奜ãŸãããã
ãã·ã³ååç©ã¯ãªãŒãœã¹ã¿ããã¯äœè¡å§çã®åŠã
äžææã®å¯äœçšãæå°éã«æå¶ããªããå åã«è¡
å§ãäœäžã§ãããããªæäžéã§æäžãã¹ãã§ã
ãã人äœã«å¯Ÿãã奜é©æäžéã¯çŽ10â200mgïŒKgã
äžå±€å¥œãŸããã¯çŽ25mgïŒKgïŒäœéïŒã§ãããçŽïŒ
mgïŒKgïŒäœéïŒãããå°ãªãæäžéã§ã¯å åãªè¡
å§éäžå¹æãåŸããããäžæ¹ãçŽ200mgïŒKgïŒäœ
éïŒãããå€ãæäžéïŒæäžæ¿åºŠïŒã§æäžããŠ
ããäžå±€å€§ããè¡å§éäžå¹æã¯åŸãããããã€äž
ææã®å¯äœçšãçããããããããåŸããæ¬çºæ
ã®çµæç©ãæäžããå Žåã«ã¯ãè¡å§éäžäœçšã¯æ
äžåŸçŽïŒâ24æéæç¶ããã§ãããã æ¬çºæã®ããïŒã€ã®æ æ§ã«ã€ããŠèª¬æãããã
ãã·ã³ãä»ã®è¡å§éäžå€ãããšãã°ãã¢ãžããžãŠ
ã¬ããã¯ã¹ïŒããšãã°ãããã¯ãããã¢ãžãïŒã
ã¬ã»ã«ãã³ãαâã¡ãã«ãããããã©ã«ã¢ãžã³ã
ã°ã¢ãããžã³ãããšããã·ãã³ãºã¢ãããã¯ãã
ãžã³ããããã©ãããŒã«ãããã»ããããšã¿ã¯ãª
ããã¯é žãã¹ãããã©ã¯ãã³ããŸãã¯ãè¬åŠçã«
蚱容ããåŸããã®å¡©ïŒããã¯çäœå ã§è§£é¢ããŠäž
èšã®ååç©ã®ãããããçããïŒããšäžç·ã«æäž
ããããšã«ãããä»å çãªè¡å§éäžå¹æãåŸãã
ãããšãèŠåºãããããã®ä»å å¹æïŒadditive
effectïŒãåŸãããã«ã¯ãåèšã®äž»è¡å§éäžå€ãš
äžç·ã«ãããã·ã³ãçŽïŒâ100mgïŒKgïŒäœéïŒã®
調åéïŒæ¿åºŠïŒã§èª¿åããã®ãæå©ã§ããããã®
ãããªåã®çµæç©ã§ã¯ãã¬ã»ã«ãã³ã¯çŽ0.007â
0.0035mgïŒKg䜿çšãããããã¯ãããã¢ãžãã¯çŽ
0.25âïŒmgïŒKg䜿çšããã¯ããã·ã³ã¯çŽ0.0014â
0.035mgïŒKg䜿çšããã®ãæå©ã§ãããæå Žåã«
ã¯ãããã·ã³ã®ä»£çšç©ãšããŠããšãã«ã¢ã©ãã³ã
䜿çšã§ããããªããªãã°ãã®ã¢ããé žã¯èèå ã§
ããã·ã³ã«å€æããããããŠè¡æ¶²æµã®äžã«æŸåºã
ããè³ã®äžã«å ¥ãããã§ãããããããªãããè¡
挿äžã®ããšãã«ã¢ã©ãã³ã®æ¿åºŠã¯ãããã·ã³ã®æ¿
床ã®çŽïŒåãããäœãå€ã§ããã¹ãã§ããããªã
ãªãã°ããã®ãããªé«ãæ¿åºŠã§ã¯è³å 移è¡æ§ã«å¯Ÿ
ããŠããšãã«ã¢ã©ãã³ã¯ããã·ã³ãšç«¶åãããã
ã·ã³ããããã·ã©ãŒãŒé µçŽ ã®äœçšã劚害ããããš
ãããåŸãããã§ãããããã«ãåèšã¢ããé žã
ã«ã«ããããäœæäžéã®ãã³ã¶ã»ãªãããŸãã¯ä»
ã®æ«æ¢¢äœçšåãã«ã«ããã·ã©ãŒãŒæå¶å€ãšäžç·ã«
ããããšã«ããããã®ã¢ããé žã®è¡å§éäžäœçšã
äžå±€å¢åŒ·ããããšãå¯èœã§ããã è³å ã®ã»ãããã³ã®éããã®ãŸãŸç¶æããããŸ
ãã¯å¢å ãããªãããããã³ãŸãã¯ãã«ãšããã
ãªã³ã®æŸåºéãå¢å ãããå¿ èŠãããå Žåã«ã¯ã
ããã·ã³ããã³ïŒãŸãã¯ããšãã«ã¢ã©ãã³ããã³
ä»çš®äžæ§ã¢ããé žã®ä»ã®ããã«ããªãããã¢ã³ã
ãå«ãçµæç©ã䜿çšããã®ãããããã®ãããªçµ
æç©ïŒãŸãã¯äžèšã¢ããé žã®çµåãïŒã¯ãæçš®ã®
æãã€ç¶æ ãŸãã¯ç¡ç é害ã®æ²»çå€ãšããŠç¹ã«æ
çšã§ãããè¡å§ãéäžãããããã«ãããªããã
ã¢ã³ãåç¬ã§ããŸãã¯ã€ã³ã·ãŠãªã³æŸåºæ§çæ°Žå
ç©ãšäžç·ã«ããã€ä»ã®ã¢ããé žãšäžç·ã«ããŸãã¯
äžç·ã§ãªã䜿çšããããšãå¯èœã§ããã åèšã®çµæç©ãå«æããã¢ããé žä»¥å€ã®äžæ§ã¢
ããé žã®äŸã«ã¯åæç¶ã¢ããé žïŒãã€ã·ã³ãã€ãœ
ãã€ã·ã³ãããªã³ïŒããã³ã¡ããªãã³ãã¹ã¬ãªã
ã³ããã¹ããžã³ããããããããããã®ã¢ããé ž
ã¯åéäœãå¡©ãŸãã¯ãšã¹ãã«ã®åœ¢ã§äœ¿çšã§ããã
ããã¯ãäœå ã§åèšã¢ããé žã«å€æãããååç©
ã®åœ¢ã§äœ¿çšã§ããããããã®ã¢ããé žã¯ãŸããé£
ç©ã®æ§ææåã®åœ¢ã§æäžããããšãã§ããã æ¬çºæãäžå±€å ·äœçã«äŸç€ºããããã«ã次ã«å®
æœäŸã瀺ããããããªããæ¬çºæã®ç¯å²ã¯æ±ºããŠ
ãããã®å®æœäŸã«èšèŒã®ç¯å²å ã®ã¿éå®ãããã
ã®ã§ã¯ãªãã äŸ ãã®å®æœäŸã¯ãè³å ã§ãã«ãšããããªã³ããè³
å ã®ããã·ã³ã®éãå¢å ãããããšã«ããåæã§
ããããšãäŸç€ºãããã®ã§ããã ãã®å®æœäŸäžã®å®éšããŒã¿ãŒã«ç€ºãããŠããã
ãã«ãè³å ã®ãã«ãšããããªã³ã®äž»ä»£è¬ç£ç©ã§ã
ãïŒâã¡ããã·âïŒâããããã·âããšãã«ãšã
ã¬ã³ã°ãªã³ãŒã«âãµã«ããšãŒãïŒMOPEGâ
SO4ïŒãã©ããã®è³å ã«èç©ãããšãã®èç©é床
ã¯ãè³å ã®ããã·ã³ã®éã®é¢æ°ã®åœ¢ã§çš®ã å€åã
ããã®ã§ããããã®ããšããæãããªããã«è³å
ã®ããã·ã³ã®éã¯ãè³å ã®ãã«ãšããããªã³ã®å
æéã®ã¿ãªããããã®ãã«ãšããããªã³ã®ã¿ãŒã³
ãªãŒããŒéããã³æŸåºéã«ã圱é¿ãäžãããã®ã§
ããã äœé150ïœã®ãªã¹ã®ã¹ãã©ã°ãŒâããŒã¬ã€ã©ã
ãããã€ãŒã«ã¹ããªããŒãããªãŒãžã³ã°ãã©ãã©
ããªãŒãºïŒãŠã€ã«ãã³ã°ãã³ãMAïŒããäŸçµŠã
ãããã®ãããã€ãããããã«å ¥ããŠé£Œè²ãã
ïŒïŒããåœãïŒâïŒå¹ïŒããããŠé£²ææ°Žããã³26ïŒ
èçœè³ªé£ŒæïŒãã€ãŒã«ã¹ããªããŒãã©ããâããŠ
ã¹âãã ã¹ã¿ãŒãã¡ã€ã³ããã³ã¹ãããªãŒããŠã©
ãŒ24RFïŒãèªç±ã«äžãããæ¯æ¥çåïŒæããç
åŸïŒæãŸã§å ç·ã300ãã€ã¯ãã¯ããïŒcm2ïŒãã¿
ãŒã©ã€ãããºããŠãŒãã¹ããã³ãŒãã¬ãŒã·ãšã³
ïŒããŒã¹ãããŒã²ã³ãN.J.ïŒè£œã®é»çã䜿çšãã
ç §å°ãããæäžå®éšã®ããã«äœ¿çšãããã©ããã¯
ïŒæ©äžçµ¶é£ããã次ãã§çå10æã«å®éšçšè¬å€æ
äžå®éšãéå§ãããã®ããœã³ã®è«æããBiochem.
Pharmacol.ã第26巻第1137é â第1142é ïŒ1977
幎ïŒãã«èšèŒã®è¬å€èª¿è£œæ¹æ³ã«åŸã€ãŠã«ã³ãã³ã²
ã«ïŒæ°Žå35ïœïŒmlïŒãçšããŠçš®ã ã®çµæã®è¬å€ã
調補ãããã¢ããé žããã³è¬åã¯ãã¹ãŠè ¹èå ã«
泚å°ããã è³å ãã€ãã³äžã®ãã«ãšããããªã³ã®åæéã
ãã³ã¿ãŒã³ãªãŒããŒéã次ã®æž¬å®æ¹æ³ã«åŸã€ãŠæž¬
å®ãããããªãã¡ãã®æž¬å®æ¹æ³ã¯ãããããã·ã
ã®æäžåŸã«ããŸãã¯ã©ãããå¯å·ç°å¢äžã«çœ®ãã
åŸã«ãMOPEGâSO4ã®èç©éã枬å®ããããšã
ããªããã®ã§ãã€ããè³ãã¢ãžããŒãäžã®
MOPEGâSO4ããã¢ããªã³äº€æã³ã©ã ããã¢ãŒ
ãã·ã¢ç€ŸïŒãã¹ã«ã¿ãŠãšãŒãN.J.ïŒè£œã®ãâ25
âDEAEâã»ãã¢ããã¯ã¹ãããçšããŠåé¢ããã
ãã®åé¢ã¯ããŒã¯ããã³ããã®æ¹æ³ããBr.J.
Pharmacol.ã第45巻第435é â第441é ïŒ1972
幎ïŒãã«åŸã€ãŠè¡ã€ãããæã ã¯åäžè©Šæã«ãã
ãŠããã·ã³ããã³MOPEGâSO4ã®äž¡è ã枬å®ã§
ããããã«äžèšåé¢æ¹æ³ãæ¹è¯ããŠçšãããåã
ã¢ãžããŒãè©ŠæïŒ0.15MâZnSO4液äžã«å ¥ããã
ã®ïŒã«ã€ããŠãæåã«ããã·ã³ãã¯ãŒã¯ã¹ããã³
ãŠãŒãã³ãã¬ã³ãã®æ¹æ³ããJ.Lab.Med.ã第50å·»
第733é â736é ïŒ1957幎ïŒãã«åŸã€ãŠå®éããã
次ãã§ãæ®ãã®ãã¢ãžããŒãã«åœéã®0.15Mâæ°Ž
é žåããªãŠã 液ãæ·»å ããåã³ãã¢ãžãã€ãºã
ãããªã³ã¯ãã³ãã€ã³ã¹ãã«ãŒã¡ã³ã瀟ïŒN.Y.ïŒ
補ã®ãããªããã³ããçšããããé å¿ãåé¢æäœ
ãè¡ãããããŠäžèšã®ã¡ãŒã¯ããã³ããã®æ¹æ³ã«
åŸã€ãŠMOPEGâSO4ãå®éãããè³ãã¢ãžããŒ
ãå šäœããã®MOPEGâSO4ããã³ããã·ã³ã®å
é¢ãååçã¯ãããã70â75ïŒ ããã³85â95ïŒ ã§
ãã€ãã ããã·ã³ãã°ã©ã³ããã¢ã€ã©ã³ãããã€ãªããž
ã«ã«ãã³ã³ãããŒïŒãã³ã°ãã¢ã€ã©ã³ããN.Y.ïŒ
補ã®ãã®ãããã³ããããã·ããã·ã°ããã±ãã«
ã«ãã³ã³ãããŒïŒã»ã³ãã«ã€ã¹ãMOïŒè£œã®ã
ã®ãã¯æ°Žã«é£æº¶æ§ã§ããã®ã§åžNaOH液ã«æº¶è§£
ããåŸãããå溶液ã«å¡©é žãå ããŠç·©è¡äœçšãè¡
ã€ãŠPH7.4ã«ããæ¢ç¥å®¹éã®é£å¡©æ°Žãå ãããã
ãã«ãã€ãŠã泚å°æ¶²ãšããŠé©åœãªåŸ®çŽ°æžæ¿æ¶²ïŒã
ã¢ã€ã³ããµã¹ãã³ãžãšã³ïŒãåŸãããã å¯å·ç°å¢ã«æŽé²ããããšãã«çããã¹ãã¬ã¹ã«
é¢ããå®éšã§ã¯ãè³å ã®ããã·ã³ã®éãå¢å ãã
ãããã«ãããã·ã³ããèªäœã®ä»£ãã«ãäžå±€æº¶ã
æããšãã«ãšã¹ãã«ã®åœ¢ã®ããã·ã³ãè©Šéšåç©ã«
æäžãããå®éšããŒã¿ãŒã®è§£æã¯ãå€æ°äžå 解æ
æ³ãŸãã¯äºæ¬¡å 解ææ³ã«åŸã€ãŠè¡ã€ãã ããããã·ãã®æäžã«ããè³å ã®MOPEGâ
SO4ã®éãã123ngïŒïœïŒåžéå€ã®ã¿ã泚å°ãã
å¯Ÿç §åç©ïŒãã175ngïŒïœãããããã·ãæäžå
ç©ãã«å¢å ããïŒïŒ°ïŒ0.001ïŒç¬¬ïŒè¡šïŒããã·ã³
ã®ã¿ã®æäžã¯è³å ã®MOPEGâSO4ã«å šã圱é¿ã
äžããªãã€ããããã®ã¢ããé žãçšããŠååŠçã
è¡ã€ãå Žåã«ã¯ãããããã·ãã«ããMOPEGâ
SO4ã®éã®å¢å 床ãäžå±€å€§ãããªããããªãã¡ã
175ngïŒKgïŒããããã·ãã®åç¬æäžãè¡ã€ãã©
ããã®å ŽåïŒãã203ngïŒïœã«å¢å ããïŒïŒ°ïŒ
0.01ïŒç¬¬è¡šïŒã
ããã®ã§ããã äžå±€è©³çŽ°ã«ããã°æ¬çºæã¯ãç¥çµã·ããã¹äžã®
ãããã³ããã³ãã«ãšããããªã³ã®éã調ç¯ïŒå¢
å ãŸãã¯æžå°ïŒããããšã«ãã人äœãåç©ã®è¡å§
éäžå€çµæç©ã«é¢ãããã®ã§ããã ç¥çµäŒéç©è³ªã§ãããããã³ããã³ãã«ãšãã
ããªã³ããžããããã·ããšãã«ã¢ã©ãã³ïŒããïŒ
ããèªå°ãããç©è³ªã§ããããšã¯æ¢ã«å ¬ç¥ã§ã
ããäžæ¹ããã¯ãã¢ããé žã§ããããã·ã³ã®é µçŽ
åŠçããããã·ã«åã«ãããã€ãã³äžã§çæãã
ãã®ã§ããããã®ããã»ã¹ã¯ãé µçŽ ã§ããããã·
ã³ããããã·ã©ãŒãŒã®è§Šåªäœçšã®ããšã§é²è¡ã
ããããã¯ãé µçŽ ã§ããâã¢ããé žãã«ã«ãã
ã·ã©ãŒãŒïŒAAADïŒã«ããè±ã«ã«ããã·ã«åã
ããŠãããã³ã«ãªãããã«ãšããããªã³ã¯ãé µçŽ
ã§ãããããã³âβâããããã·ã©ãŒãŒããå«ã
ãã€ãã³äžã§ãããã³ããçããããã®äžé£ã®å
å¿ã«ãããŠãåŸé段éã¯ããã·ã³ãããããžã®å€
æ段éã§ããããã®çç±ã®ããã«ãããŒãã³ãœã³
ç ã®åŠããããã³æ¬ ä¹æ§çŸç ã«èµ·å³ãã身äœé害
éšãæããæ£è ã«ãããã³æäžãè¡ãªãããããš
ããã€ããããããªããéœåã®æªãããšã«ã¯ãã
ããæäžãããšããã¯èº«äœå šäœã®çŽ°èã«åžåãã
ãŠãããã³ã«å€ãããããã«ãã€ãŠããããã®çŽ°
èã«ãããæ£åžžãªä»£è¬ããã»ã¹ã劚害ããããšã
ãäžéœåãªäºæ ãçããã®ã§ãããããã«ãã
ã¯ãç¥çµäŒéç©è³ªã§ããã»ãããã³ã®æ£åžžãªäººäœ
å èç©ã劚害ãããã€ãâã¢ããã·ã«ã¡ããªã
ã³ååç©ã®è³å ååšéãäœäžãããããããã®äž
ææã®å¯äœçšã®ããã«æ£è ã«ããããããªã³âãª
ãçŸè±¡ãçãèªããããããšãããããããŠæå Ž
åã«ã¯ç²Ÿç¥ç ç城åãèªããããããšããããåŸ
ããã·ããã¹äžã®ãããã³ããã³ãã«ãšããããª
ã³ã®éãå¢å ãããäœçšãæããä»çš®è¬å€ã®äŸã«
ã¯ã¢ãã¢ãã³ãªãã·ããŒãŒæå¶å€ïŒããã¯åèšã®
ç¥çµäŒéç©è³ªã®å解ãé 延ããããã®ã§ããïŒã
ãã³ïŒæ žåã®ææãã€å€ïŒã¢ã³ãããã¬ãµã³ãïŒ
ããããããããããã®ååç©ã¯æå§çç¶ã䌎ã
çŸç ã®æ²»çå€ãšããŠäœ¿çšãããŠãããããããã
ãŸããã·ããã¹äžã®ãããã³ããã³ãã«ãšããã
ãªã³ã®éã®å¢å äœçšã®ä»ã«æ¯èŒçéç¹ç°æ§ã®ååŠ
çäœçšãæãããã®ã§ãã€ãŠãããªãã¡çš®ã ã®å¯
äœçšãæããããšãã°è¡å§äžæäœçšçãæããã
ããããŠãã®è¡å§äžæã¯ãã¢ãã¢ãã³ãªãã·ããŒ
ãŒæå¶å€ãæäžããæ£è ãæçš®ã®é£åãé£ã¹ããš
ãçã«èµ·ããã®ã§ããã ãã¹ãâã·ããããã¯ãããã³âããã³ãã«ãš
ããããªã³âã¬ã»ãã¿ãŒãçŽæ¥ã«æŽ»æ§åãããè¬
å€ãæäžããããšã«ããããããããŒãžãã¯
ïŒdopaminergicïŒâããã³ãã«ã¢ãã¬ããŒãžãã¯
ã·ããã¹ãééããä¿¡å·ã®äŒéæ§ãé«ããããšã
ã§ããããã®ãããªè¬å€ã®äŸã«ã¯æ¬¡ã®ãã®ããã
ãããïŒã¢ãã¢ã«ãããããã¢ã¯ãªããã³ïŒãã
ãã³ãªã»ãã¿ãŒïŒãã¯ãããžã³ãαâã¡ãã«ãã
ïŒåååãã¢ã«ãã¡ãããââããã¯è³å ã§Î±âã¡
ãã«ãã«ãšããããªã³ã«å€æãããïŒïŒãã«ãšã
ãããªã³ã¬ã»ãã¿ãŒïŒããããã®ååç©ã¯æ¢è¿°ã®
ä»çš®è¬å€ãšåæ§ã«ãè³ããã³ä»ã®äœå çµæå šäœã«
ãããŠå¯Ÿå¿ã¬ã»ãã¿ãŒäžã§äœçšãããã®ããã«äž
ææã®å¯äœçšã瀺ããã®ã§ããã ã·ããã¹äžã«ãããã³ãŸãã¯ãã«ãšããããªã³
ãéå°éååšãããšãã«èµ·ãä»çš®çŸç ã®äŸã«ã¯æ¬¡
ã®ãã®ããããããïŒç²Ÿç¥ç ïŒãããã³ã®éã極
端ã«å€ãïŒãéåé害çïŒmovement disordersïŒ
ããšãã°ã¿ãŒãžãã»ãžã¹ããã·ã¢çããã³ã®ã¬
ã¹ãããã©ãããŠã¬ããçå矀ïŒãããã³ã®éã
極端ã«å€ãïŒïŒé«è¡å§ããã³äžæŽèïŒäº€æç¥çµã
ã€ãã³ããæŸåºããããã«ãšããããªã³ã®éã極
端ã«å€ãïŒãçŸåšãããã®ç æ°ã®æ²»çã¯äžè¬ã«ã
ãããã³ãŸãã¯ãã«ãšããããªã³ãšãã®åŸæã¬ã»
ãã¿ãŒïŒportâreceptorsïŒãšã®ã€ã³ã¿ãŒã©ã¯ã·
ãšã³ã劚害ããè¬å€ïŒããšãã°ããšããã¢ãžã³ãŸ
ãã¯ãããããšãã³ïŒãçšããŠè¡ãªãããŠããã
ããããªãããããã®è¬å€ã¯ãã¹ãŠãè¥å¹²ã®éç¹
ç°æ§äœçšãè¡šãããã®ã§ãã€ãŠããããã€ãŠãã®
æçšæã«å¯äœçšãè¡šãããããšãããã ç¥çµäžã®ããã·ã³ã®éãå€ããããšã«ãããã
ãã³ãŸãã¯ãã«ãšããããªã³ã®éãå¢å ãŸãã¯æž
å°ãããè©Šã¿ã以åã«è¡ãªããããããã®è©Šã¿ã¯
æåããªãã€ãããªããªãã°è³ããã³çš®ã ã®çµæ
ã®äžã®ãããã®ååç©ã®éãå€åãããããšã¯è¡
ãããªãã€ãããã§ãããè³å ã®ããã®æ¿åºŠã¯ã
æå®ã®å®éšæ¡ä»¶äžã§ã¯ãããã³ããã³ãã«ãšãã
ããªã³ã®åæé床ã«æ¯äŸããŠå€åãããããŠè³å
ã®ããã®æ¿åºŠã¯ãè³å ã®ããã·ã³ã®æ¿åºŠã®å¢å ã«
ããå¢å ãããããšãã§ãããã€ãè³å ã®ããã®
æ¿åºŠã¯ãè³å ã®ããã·ã³ã®æ¿åºŠãäœäžããããã
ãªåŠçã«ãã€ãŠäœäžãããããšãã§ããïŒã©ãã
ãçšããå®éšïŒããšãæåã«èŠåºããç 究è ã¯ã¯
ãŒããã³ã§ãããããµã€ãšã³ã¹ã第185å·»183é â
第184é ïŒ1974幎ïŒæ12æ¥ïŒããè³å ã®ããã·ã³ã®
éãå¢å ãããçºã®åŠçæ¹æ³ã®ïŒã€ã¯ãããã·ã³
ããèªäœãæäžããããšã§ãã€ããè³å ã®ããã·
ã³ã®éãæžå°ãããçºã®åŠçæ¹æ³ã®ïŒã€ã¯ãè¡æŒ¿
äžã®ããã·ã³ïŒãã©ãºãããã·ã³ïŒã®è³å 移è¡æ§
ãšç«¶åããæ§è³ªãæããä»çš®äžæ§ã¢ããé žã®ãã¡
ã®ïŒã€ïŒäŸãã°ãã€ã·ã³ïŒãæäžããããšã§ã
ãããã®åŠèª¬ãçºè¡šããã以åã«ã¯ãåèšã®åŸé
段éã®åå¿ãé²è¡ãããé µçŽ ã§ããããã·ã³ãã
ããã·ã©ãŒãŒã¯ããã·ã³ã«ããé«åºŠé£œåç¶æ ã«ãª
ã€ãŠããã®ã§ãè³å ã®ããã·ã³ã®éã®å¢å ãŸãã¯
æžå°ãããã·ã³ãããããžã®å€æåå¿ã«åœ±é¿ãäž
ããããšã¯ãªãã§ããããšæãããŠããã®ã§ã
ããäžæ¹äžèšã®ã¯ãŒããã³çã®è«æãŸãã¯å ¶åŸã«
çºè¡šãããã®ããœã³åã³ã¯ãŒããã³ã®è«æ
ããBiochem.Pharmacologyã第26巻第1137é â
第1142é ïŒ1977幎ïŒæå·ïŒã«ã¯ãããèç©éã«é¢
ããåèšã®å€åã¯ãè³å ã®ãããã³ãŸãã¯ãã«ãš
ããããªã³ã®éã®å€åã䌎ããã®ã§ããããšã¯å š
ãé瀺ãããŠããªãããŸããè³å ã®ããã·ã³ã®é
ãå€ããããšã«ãããã·ããã¹ãžã®ãããã³ãŸã
ã¯ãã«ãšããããªã³ã®æŸåºéã«åœ±é¿ãäžããããš
ãã§ããããšããäžèšã®æç®ã«ã¯å šãé瀺ãããŠ
ããªãã ã·ããã¹äžã«å®éã«ååšãããããã³ããã³ïŒ
ãŸãã¯ãã«ãšããããªã³ã®éãå¢å ãŸãã¯æžå°ã
ããæ段ãéçºããããšã¯ãéåžžã«å¥œãŸããããš
ã§ããããã€ãã³äžã«è²¯èµãããååŠäŒéç©è³ª
ïŒããªãã¡ã·ããã¹äŒéç©è³ªïŒã®ãã¹ãŠã®ååã
çããã·ããã¹ã«å®¹æã«æŸåºã§ãããã®ãšã¯éã
ãªããšããããšãçŸåšå ¬ç¥ã§ãããããã·ããã¹
äžã§ã®è©²ååŠäŒéç©è³ªã®éçå€åã«äŒŽã€ãŠãè³ãŸ
ãã¯ä»ã®çµç¹ã®äžã®ãããã³ãŸãã¯ãã«ãšããã
ãªã³ã®å šéãå€åãããšã¯éããªããåèšã®ã
ããMAOæå¶å€ãããšããã¢ãžã³ããã³ä»ã®è¬
å€ã®æäžæã«äŒŽããããªäžææã®å¯äœçšããªãã
ãã€çååŠçç¹ç°æ§ãæãããããªæ段ãéçºã
ãã®ãæãŸããã®ã§ããããã®ãããªæ段ã¯ãã
ãèªäœãç æ°ã®ããã®æçšãªæ²»çæ段ãšããŠå©çš
ã§ããã§ãããããããã¯ãçš®ã ã®è¬å€ã®æ²»çå¹
æãäžå±€é«ããããã«ãåèšã®æ段ã¯è©²è¬å€ãšçµ
åãããŠå©çšã§ããã§ãããã çŸåšãè¡å§éäžå€ãšããŠæãåºã䜿çšãããŠã
ãå»è¬åã®ãã¡è¥å¹²ã®ãã®ãããšãã°ãαâã¡ã
ã«ããïŒã¢ã«ãã¡ããïŒã11ïŒ17αâãžã¡ããã·
â18βâãïŒïŒïŒïŒïŒïŒâããªã¡ããã·ãã³ãŸã€
ã«ïŒãªãã·ã3βïŒ20αâãšãã³ãã³â16βâã«ã«
ãã³é žã¡ãã«ãšã¹ãã«ïŒã¬ã»ã«ãã³ïŒãïŒâïŒïŒïŒ
ïŒâãžã¯ããããšãã«ã¢ããïŒâïŒâã€ãããŸãª
ã³ãã€ããã¯ãã©ã€ãïŒã¯ãããžã³ãã€ããã¯ã
ã©ã€ãïŒçã¯ã人äœå ã§ããã©ã¯ãã³ã®åæ³ãåº
æãããã®ã§ããããã®å¯äœçšã¯å¥œãŸãããªãã
ã®ã§ããããªããªãã°ãããã©ã¯ãã³ã®åŸªç°éã®
å¢å€§ã¯æçš®ã®èºã¬ã³ã®æ¡å€§ãä¿é²ãããã€ç·æ§ã«
ã¯é°èã®åå ãšãªãåŸãããšãæè¿å ±åãããã
ãã§ããããããã€ãŠãçŸåšã®æ²»çæ³ã®ä»£ãã«å©
çšã§ãããããã¯çŸåšã®æ²»çæ³ã®è£åæ²»çæ³ãšã
ãŠå©çšã§ãããã€ããã©ã¯ãã³ã®åæ³ãä¿é²ããª
ããããªé«è¡å§éäžæ²»çæ³ãéçºããããšãéåžž
ã«æãŸããã®ã§ããã æ¬çºæã¯äžæ¢ç¥çµç³»ã®ã·ããã¹äžã®ãã«ãšãã
ããªã³ã®éïŒçžå¯ŸéïŒã®äœäžã«äŒŽãé«è¡å§çã®ã
ãã®è¡å§éäžå€çµæç©ãæäŸãããã®ã§ãããç¥
çµäžã®ããã·ã³ã®éãå¢å ãŸãã¯æžå°ããããã
ãªåŠçã¯ãã·ããã¹äžã®ãããã³ãŸãã¯ãã«ãšã
ãããªã³ã®æŸåºéã®å¢å ãŸãã¯æžå°ãããããã
ã®ã§ãããããããŠåŸè ã®å Žåã®å¢å éãŸãã¯æž
å°éã¯ãããããåè ã®å Žåã®å¢å éãŸãã¯æžå°
éã«å¯Ÿå¿ããå€ã§ããããšãæ¬çºæè ãæ€åºŠèŠåº
ãããã®çºèŠã«åºããŠæ¬çºæãå®æãããã®ã§ã
ããããã·ã³ããã®ãã¬ã«ãŒãµãŒïŒåé§äœïŒããš
ãã°ããšãã«ã¢ã©ãã³ãŸãã¯ä»ã®äžæ§ã¢ããé žã¯
åç¬ãŸãã¯æ··åç©ã®åœ¢ã§ããã€ä»ã®è¬å€ãšäžç·
ã«ããŸãã¯äžç·ã«ããã«æäžã§ããããã«ãã€
ãŠãè³å ã®ããã·ã³ïŒããã³ããšãã«ã¢ã©ãã³ïŒ
ã®éãå¢å ãŸãã¯æžå°ãããããšãã§ããããã
ãã®æäžã«ãã€ãŠãäžæ¢ç¥çµç³»ã®ã·ããã¹äžã®ã
ã«ãšããããªã³ã®äžè¶³ã«èµ·å ããé«è¡å§çãæ²»ç
ã§ãããåæ§ã«ãåèšæ··åç©äžã®ããªãããã¢ã³
ãŸãã¯ä»ã®ã¢ããé žã®ååšå²åãçš®ã å€ããããš
ã«ããããããã¯ããªãããã¢ã³ãä»ã®ã¢ããé ž
ãšäžç·ã«ããã«æäžããããšã«ããè³å ã®ã»ãã
ãã³ãŸãã¯ä»ã®ç¥åŸäŒéç©è³ªã®åæéããã³ã·ã
ãã¹ãžã®ãã®æŸåºéã調ç¯ã§ãããã»ãããã³å
æéã®å¢å ã«ããè¡å§ãäœäžãããããšãå¯èœã§
ãããã»ãããã³åæéãå¢å ãããããã«ããª
ãããã¢ã³ã䜿çšããããšã¯ãå¥ã®ã¢ããé žã§ã
ãïŒâããããã·ããªãããã¢ã³ïŒããã¯é£ç©äž
ã«ååšããããã€éåžžã¯äººäœå ã§æ¶è²»ãããªãã
ã®ã§ããïŒã䜿çšããããšãããäžå±€å¥œãŸããã
ãšã§ããããªããªãã°ããªãããã¢ã³ã¯ãã€ãã³
äžã§ã»ãããã³ã«å€æãããããããŠãã®ãã€ã
ã³ã¯éåžžã»ãããã³ïŒããã¯äŒéç©è³ªã®ïŒçš®ã§ã
ãïŒãåæãããšããã§ãããäžæ¹ãïŒâããã
ãã·ããªãããã¢ã³ã¯çš®ã ã®åã®çŽ°èã®äžã§éç¹
ç°çã«ã»ãããã³ã«å€æããåŸããã®ã§ãã€ãŠã
ãã®ããã«çš®ã ã®å¯äœçšãçããããšãããåŸã
ããã§ããããã«ãšããããªã³æŸåºæ§ã®ãã€ãã³
ãç¹ã«é«æŽ»æ§ã®ãã®ãåŠããšããããšã¯ç¡é¢ä¿ã«
ããã·ã³ã®æäžã«ããã·ããã¹äžã®ãã«ãšããã
ãªã³ã®éãå¢å ãããããšãã§ãããè³å ã®ããª
ãããã¢ã³ã®éãæžå°ãŸãã¯å¢å ãããããšã«ã
ããã»ãããã³æŸåºéãæžå°ãŸãã¯å¢å ãããã
ãšãã§ãããæå®ã®äžæ§ã¢ããé žæ··åç©ã®äžã®ã
ãã·ã³ã®ååšæ¯çã調æŽããããšã«ããããã«ãš
ããããªã³ã®æŸåºéãå¢å ãŸãã¯æžå°ãããããš
ãã§ãããå°éæäžã®å Žåã«ã¯ãããã·ã³ã®ä»£ã
ã«ããšãã«ã¢ã©ãã³ã䜿çšããããšãã§ãããåŸ
èšã®åŠãããã«ãšããããªã³ã®æŸåºéã調ç¯ããª
ããã·ããã¹ãžã®ã»ãããã³ã®æŸåºéã調ç¯ãã
ããã«ãåèšäžæ§ã¢ããé žæ··åç©äžã«ååšãã
ãããªãããã¢ã³ã®éšåããå©çšããããšãã§ã
ãããããã®ã¢ããé žã¯ãéé¢ã¢ããé žãå¡©ããš
ã¹ãã«ãããããã®åœ¢ã§æäžã§ãããŸãã¯äœå ã§
ã¢ããé žã«å€æãããååç©ïŒããšãã°Î±âã±ã
é žïŒã®åœ¢ã§æäžã§ãããããŠãã®æäžã¯ãè ¹èå
æäžãç®äžæäžãçèå æäžãŸãã¯çµå£æäžã®åœ¢
ã§è¡ãããšãã§ããã æ¬çºæã«åŸãã°ãããã·ã³ããã³ïŒãŸãã¯ãã
ã·ã³ãã¬ã«ãŒãµãŒïŒããšãã°ããšãã«ã¢ã©ãã³ïŒ
ããã³ïŒãŸãã¯ä»ã®äžæ§ã¢ããé žãåç¬ã§ããŸã
ã¯ïŒçš®ãŸãã¯ãã以äžã®å ¬ç¥è¡å§éäžè¬å€ãšçµå
ããŠæ£è ã«æäžãããããã«ãã€ãŠãã·ããã¹ãž
ã®ãã«ãšããããªã³ã®æŸåºéãå¢å ãããããšã
ã§ãããåæã«ãããªãããã¢ã³ã®åç¬æäžã«ã
ãããããã¯ã¢ããé žæ··åç©äžã®ããªãããã¢ã³
ã®ååšæ¯çãçš®ã å€ããããšã«ãããã»ãããã³
ã®æŸåºéãå¶åŸ¡ã§ããããã«ãšããããªã³æŸåºæ§
ãã€ãã³ãŸãã¯ã»ãããã³æŸåºæ§ãã€ãã³ãç¹ã«
é«æŽ»æ§ã®ãã®ã§ãããåŠããšããããšã¯ç¡é¢ä¿
ã«ãã¢ããé žæ··åç©ã䜿çšããããšã«ãããã·ã
ãã¹ãžã®ãã«ãšããããªã³ãŸãã¯ã»ãããã³ã®æŸ
åºéãçš®ã å€ããããšãã§ãããåæ§ã«ãããã·
ã³ãŸãã¯ããªãããã¢ã³ã®è³å 移è¡æ§ïŒç§»è¡éïŒ
ãšç«¶åãåŸã移è¡æ§ãæããã¢ããé žæ··åç©ãæ
äžããŠè³å ã®ããã·ã³ãŸãã¯ããªãããã¢ã³ã®é
ãæžå°ãããããšã«ããããã«ãšããããªã³ãŸã
ã¯ã»ãããã³ã®æŸåºéãæžå°ã§ããããã«ãã€
ãŠãããšãã°äžæ¢ç¥çµç³»ã«èµ·å ããäœè¡å§çã«æ©
ãæ£è ãæ²»çã§ããã ããã·ã³ã®è¡å§éäžäœçšã®æ£ç¢ºãªã¡ã«ããºã ã¯
æªã å€ã€ãŠããªãããã©ããçäœãžã®ããã·ã³ã®
å šäœçšã¯ãã¢ã«ãã¡ãããã¯ãããžã³ãã€ããã¯
ãã©ã€ããŸãã¯ã¬ã»ã«ãã³ã®äœçšãšã¯çžç°ãªãã
ã®ã§ãããšæãããããªããªãã°ããã·ã³ã¯ãã
ã©ã¯ãã³ã®åæ³ãå¢å ãããªãããã§ããã æ¬çºæã®çµæç©ã¯çµå£æäžãè ¹èå æäžãç®äž
æäžãéèå æäžãŸãã¯çèå æäžã«ããæäžã§
ããããã®ã¢ããé žã¯ãã®ãŸãŸã®åœ¢ã§äœ¿çšã§ãã
ãããã¯å¡©ãŸãã¯ãšã¹ãã«ãŸãã¯ããããã®åœ¢ã§
䜿çšã§ãããããã¯ãçäœå ã§ã®ä»£è¬äœçšã«ãã
ã¢ããé žã«å€æã§ããååç©ïŒããšãã°Î±âã±ã
ã¢ããé žïŒã®åœ¢ã§äœ¿çšã§ãããããã¯ãã€ã³ã·ãŠ
ãªã³ã»ãããã³ãèªãåºãããšã«ããè³å åžåæ§
ãå€ããããšãã§ãããããªçæ°Žåç©ãšäžç·ã«ã
ãŸãã¯äžç·ã«ããã«æäžã§ããããã®çµæç©ã¯æ°Ž
ãŸãã¯æžèé£å¡©æº¶æ¶²ã®åŠãä»»æã®ç¡å®³ããã¯ã«ã«
溶解ãŸãã¯æ··åããŠäœ¿çšãããããŸãã¯åžžçšåºäœ
åžéå€ãŸãã¯æ äœãå«ãé å€ãŸãã¯ç²å€ã®åœ¢ã§äœ¿
çšããã®ã䟿å©ã§ãããè¡å§éäžå€ãšããŠäœ¿çšã
ãå Žåã«ã¯ããã®çµæç©ã¯ãäžææã®å¯äœçšãé²
æ¢ã§ãããããªæ¿åºŠã§æäžããã®ã奜ãŸãããã
ãã·ã³ååç©ã¯ãªãŒãœã¹ã¿ããã¯äœè¡å§çã®åŠã
äžææã®å¯äœçšãæå°éã«æå¶ããªããå åã«è¡
å§ãäœäžã§ãããããªæäžéã§æäžãã¹ãã§ã
ãã人äœã«å¯Ÿãã奜é©æäžéã¯çŽ10â200mgïŒKgã
äžå±€å¥œãŸããã¯çŽ25mgïŒKgïŒäœéïŒã§ãããçŽïŒ
mgïŒKgïŒäœéïŒãããå°ãªãæäžéã§ã¯å åãªè¡
å§éäžå¹æãåŸããããäžæ¹ãçŽ200mgïŒKgïŒäœ
éïŒãããå€ãæäžéïŒæäžæ¿åºŠïŒã§æäžããŠ
ããäžå±€å€§ããè¡å§éäžå¹æã¯åŸãããããã€äž
ææã®å¯äœçšãçããããããããåŸããæ¬çºæ
ã®çµæç©ãæäžããå Žåã«ã¯ãè¡å§éäžäœçšã¯æ
äžåŸçŽïŒâ24æéæç¶ããã§ãããã æ¬çºæã®ããïŒã€ã®æ æ§ã«ã€ããŠèª¬æãããã
ãã·ã³ãä»ã®è¡å§éäžå€ãããšãã°ãã¢ãžããžãŠ
ã¬ããã¯ã¹ïŒããšãã°ãããã¯ãããã¢ãžãïŒã
ã¬ã»ã«ãã³ãαâã¡ãã«ãããããã©ã«ã¢ãžã³ã
ã°ã¢ãããžã³ãããšããã·ãã³ãºã¢ãããã¯ãã
ãžã³ããããã©ãããŒã«ãããã»ããããšã¿ã¯ãª
ããã¯é žãã¹ãããã©ã¯ãã³ããŸãã¯ãè¬åŠçã«
蚱容ããåŸããã®å¡©ïŒããã¯çäœå ã§è§£é¢ããŠäž
èšã®ååç©ã®ãããããçããïŒããšäžç·ã«æäž
ããããšã«ãããä»å çãªè¡å§éäžå¹æãåŸãã
ãããšãèŠåºãããããã®ä»å å¹æïŒadditive
effectïŒãåŸãããã«ã¯ãåèšã®äž»è¡å§éäžå€ãš
äžç·ã«ãããã·ã³ãçŽïŒâ100mgïŒKgïŒäœéïŒã®
調åéïŒæ¿åºŠïŒã§èª¿åããã®ãæå©ã§ããããã®
ãããªåã®çµæç©ã§ã¯ãã¬ã»ã«ãã³ã¯çŽ0.007â
0.0035mgïŒKg䜿çšãããããã¯ãããã¢ãžãã¯çŽ
0.25âïŒmgïŒKg䜿çšããã¯ããã·ã³ã¯çŽ0.0014â
0.035mgïŒKg䜿çšããã®ãæå©ã§ãããæå Žåã«
ã¯ãããã·ã³ã®ä»£çšç©ãšããŠããšãã«ã¢ã©ãã³ã
䜿çšã§ããããªããªãã°ãã®ã¢ããé žã¯èèå ã§
ããã·ã³ã«å€æããããããŠè¡æ¶²æµã®äžã«æŸåºã
ããè³ã®äžã«å ¥ãããã§ãããããããªãããè¡
挿äžã®ããšãã«ã¢ã©ãã³ã®æ¿åºŠã¯ãããã·ã³ã®æ¿
床ã®çŽïŒåãããäœãå€ã§ããã¹ãã§ããããªã
ãªãã°ããã®ãããªé«ãæ¿åºŠã§ã¯è³å 移è¡æ§ã«å¯Ÿ
ããŠããšãã«ã¢ã©ãã³ã¯ããã·ã³ãšç«¶åãããã
ã·ã³ããããã·ã©ãŒãŒé µçŽ ã®äœçšã劚害ããããš
ãããåŸãããã§ãããããã«ãåèšã¢ããé žã
ã«ã«ããããäœæäžéã®ãã³ã¶ã»ãªãããŸãã¯ä»
ã®æ«æ¢¢äœçšåãã«ã«ããã·ã©ãŒãŒæå¶å€ãšäžç·ã«
ããããšã«ããããã®ã¢ããé žã®è¡å§éäžäœçšã
äžå±€å¢åŒ·ããããšãå¯èœã§ããã è³å ã®ã»ãããã³ã®éããã®ãŸãŸç¶æããããŸ
ãã¯å¢å ãããªãããããã³ãŸãã¯ãã«ãšããã
ãªã³ã®æŸåºéãå¢å ãããå¿ èŠãããå Žåã«ã¯ã
ããã·ã³ããã³ïŒãŸãã¯ããšãã«ã¢ã©ãã³ããã³
ä»çš®äžæ§ã¢ããé žã®ä»ã®ããã«ããªãããã¢ã³ã
ãå«ãçµæç©ã䜿çšããã®ãããããã®ãããªçµ
æç©ïŒãŸãã¯äžèšã¢ããé žã®çµåãïŒã¯ãæçš®ã®
æãã€ç¶æ ãŸãã¯ç¡ç é害ã®æ²»çå€ãšããŠç¹ã«æ
çšã§ãããè¡å§ãéäžãããããã«ãããªããã
ã¢ã³ãåç¬ã§ããŸãã¯ã€ã³ã·ãŠãªã³æŸåºæ§çæ°Žå
ç©ãšäžç·ã«ããã€ä»ã®ã¢ããé žãšäžç·ã«ããŸãã¯
äžç·ã§ãªã䜿çšããããšãå¯èœã§ããã åèšã®çµæç©ãå«æããã¢ããé žä»¥å€ã®äžæ§ã¢
ããé žã®äŸã«ã¯åæç¶ã¢ããé žïŒãã€ã·ã³ãã€ãœ
ãã€ã·ã³ãããªã³ïŒããã³ã¡ããªãã³ãã¹ã¬ãªã
ã³ããã¹ããžã³ããããããããããã®ã¢ããé ž
ã¯åéäœãå¡©ãŸãã¯ãšã¹ãã«ã®åœ¢ã§äœ¿çšã§ããã
ããã¯ãäœå ã§åèšã¢ããé žã«å€æãããååç©
ã®åœ¢ã§äœ¿çšã§ããããããã®ã¢ããé žã¯ãŸããé£
ç©ã®æ§ææåã®åœ¢ã§æäžããããšãã§ããã æ¬çºæãäžå±€å ·äœçã«äŸç€ºããããã«ã次ã«å®
æœäŸã瀺ããããããªããæ¬çºæã®ç¯å²ã¯æ±ºããŠ
ãããã®å®æœäŸã«èšèŒã®ç¯å²å ã®ã¿éå®ãããã
ã®ã§ã¯ãªãã äŸ ãã®å®æœäŸã¯ãè³å ã§ãã«ãšããããªã³ããè³
å ã®ããã·ã³ã®éãå¢å ãããããšã«ããåæã§
ããããšãäŸç€ºãããã®ã§ããã ãã®å®æœäŸäžã®å®éšããŒã¿ãŒã«ç€ºãããŠããã
ãã«ãè³å ã®ãã«ãšããããªã³ã®äž»ä»£è¬ç£ç©ã§ã
ãïŒâã¡ããã·âïŒâããããã·âããšãã«ãšã
ã¬ã³ã°ãªã³ãŒã«âãµã«ããšãŒãïŒMOPEGâ
SO4ïŒãã©ããã®è³å ã«èç©ãããšãã®èç©é床
ã¯ãè³å ã®ããã·ã³ã®éã®é¢æ°ã®åœ¢ã§çš®ã å€åã
ããã®ã§ããããã®ããšããæãããªããã«è³å
ã®ããã·ã³ã®éã¯ãè³å ã®ãã«ãšããããªã³ã®å
æéã®ã¿ãªããããã®ãã«ãšããããªã³ã®ã¿ãŒã³
ãªãŒããŒéããã³æŸåºéã«ã圱é¿ãäžãããã®ã§
ããã äœé150ïœã®ãªã¹ã®ã¹ãã©ã°ãŒâããŒã¬ã€ã©ã
ãããã€ãŒã«ã¹ããªããŒãããªãŒãžã³ã°ãã©ãã©
ããªãŒãºïŒãŠã€ã«ãã³ã°ãã³ãMAïŒããäŸçµŠã
ãããã®ãããã€ãããããã«å ¥ããŠé£Œè²ãã
ïŒïŒããåœãïŒâïŒå¹ïŒããããŠé£²ææ°Žããã³26ïŒ
èçœè³ªé£ŒæïŒãã€ãŒã«ã¹ããªããŒãã©ããâããŠ
ã¹âãã ã¹ã¿ãŒãã¡ã€ã³ããã³ã¹ãããªãŒããŠã©
ãŒ24RFïŒãèªç±ã«äžãããæ¯æ¥çåïŒæããç
åŸïŒæãŸã§å ç·ã300ãã€ã¯ãã¯ããïŒcm2ïŒãã¿
ãŒã©ã€ãããºããŠãŒãã¹ããã³ãŒãã¬ãŒã·ãšã³
ïŒããŒã¹ãããŒã²ã³ãN.J.ïŒè£œã®é»çã䜿çšãã
ç §å°ãããæäžå®éšã®ããã«äœ¿çšãããã©ããã¯
ïŒæ©äžçµ¶é£ããã次ãã§çå10æã«å®éšçšè¬å€æ
äžå®éšãéå§ãããã®ããœã³ã®è«æããBiochem.
Pharmacol.ã第26巻第1137é â第1142é ïŒ1977
幎ïŒãã«èšèŒã®è¬å€èª¿è£œæ¹æ³ã«åŸã€ãŠã«ã³ãã³ã²
ã«ïŒæ°Žå35ïœïŒmlïŒãçšããŠçš®ã ã®çµæã®è¬å€ã
調補ãããã¢ããé žããã³è¬åã¯ãã¹ãŠè ¹èå ã«
泚å°ããã è³å ãã€ãã³äžã®ãã«ãšããããªã³ã®åæéã
ãã³ã¿ãŒã³ãªãŒããŒéã次ã®æž¬å®æ¹æ³ã«åŸã€ãŠæž¬
å®ãããããªãã¡ãã®æž¬å®æ¹æ³ã¯ãããããã·ã
ã®æäžåŸã«ããŸãã¯ã©ãããå¯å·ç°å¢äžã«çœ®ãã
åŸã«ãMOPEGâSO4ã®èç©éã枬å®ããããšã
ããªããã®ã§ãã€ããè³ãã¢ãžããŒãäžã®
MOPEGâSO4ããã¢ããªã³äº€æã³ã©ã ããã¢ãŒ
ãã·ã¢ç€ŸïŒãã¹ã«ã¿ãŠãšãŒãN.J.ïŒè£œã®ãâ25
âDEAEâã»ãã¢ããã¯ã¹ãããçšããŠåé¢ããã
ãã®åé¢ã¯ããŒã¯ããã³ããã®æ¹æ³ããBr.J.
Pharmacol.ã第45巻第435é â第441é ïŒ1972
幎ïŒãã«åŸã€ãŠè¡ã€ãããæã ã¯åäžè©Šæã«ãã
ãŠããã·ã³ããã³MOPEGâSO4ã®äž¡è ã枬å®ã§
ããããã«äžèšåé¢æ¹æ³ãæ¹è¯ããŠçšãããåã
ã¢ãžããŒãè©ŠæïŒ0.15MâZnSO4液äžã«å ¥ããã
ã®ïŒã«ã€ããŠãæåã«ããã·ã³ãã¯ãŒã¯ã¹ããã³
ãŠãŒãã³ãã¬ã³ãã®æ¹æ³ããJ.Lab.Med.ã第50å·»
第733é â736é ïŒ1957幎ïŒãã«åŸã€ãŠå®éããã
次ãã§ãæ®ãã®ãã¢ãžããŒãã«åœéã®0.15Mâæ°Ž
é žåããªãŠã 液ãæ·»å ããåã³ãã¢ãžãã€ãºã
ãããªã³ã¯ãã³ãã€ã³ã¹ãã«ãŒã¡ã³ã瀟ïŒN.Y.ïŒ
補ã®ãããªããã³ããçšããããé å¿ãåé¢æäœ
ãè¡ãããããŠäžèšã®ã¡ãŒã¯ããã³ããã®æ¹æ³ã«
åŸã€ãŠMOPEGâSO4ãå®éãããè³ãã¢ãžããŒ
ãå šäœããã®MOPEGâSO4ããã³ããã·ã³ã®å
é¢ãååçã¯ãããã70â75ïŒ ããã³85â95ïŒ ã§
ãã€ãã ããã·ã³ãã°ã©ã³ããã¢ã€ã©ã³ãããã€ãªããž
ã«ã«ãã³ã³ãããŒïŒãã³ã°ãã¢ã€ã©ã³ããN.Y.ïŒ
補ã®ãã®ãããã³ããããã·ããã·ã°ããã±ãã«
ã«ãã³ã³ãããŒïŒã»ã³ãã«ã€ã¹ãMOïŒè£œã®ã
ã®ãã¯æ°Žã«é£æº¶æ§ã§ããã®ã§åžNaOH液ã«æº¶è§£
ããåŸãããå溶液ã«å¡©é žãå ããŠç·©è¡äœçšãè¡
ã€ãŠPH7.4ã«ããæ¢ç¥å®¹éã®é£å¡©æ°Žãå ãããã
ãã«ãã€ãŠã泚å°æ¶²ãšããŠé©åœãªåŸ®çŽ°æžæ¿æ¶²ïŒã
ã¢ã€ã³ããµã¹ãã³ãžãšã³ïŒãåŸãããã å¯å·ç°å¢ã«æŽé²ããããšãã«çããã¹ãã¬ã¹ã«
é¢ããå®éšã§ã¯ãè³å ã®ããã·ã³ã®éãå¢å ãã
ãããã«ãããã·ã³ããèªäœã®ä»£ãã«ãäžå±€æº¶ã
æããšãã«ãšã¹ãã«ã®åœ¢ã®ããã·ã³ãè©Šéšåç©ã«
æäžãããå®éšããŒã¿ãŒã®è§£æã¯ãå€æ°äžå 解æ
æ³ãŸãã¯äºæ¬¡å 解ææ³ã«åŸã€ãŠè¡ã€ãã ããããã·ãã®æäžã«ããè³å ã®MOPEGâ
SO4ã®éãã123ngïŒïœïŒåžéå€ã®ã¿ã泚å°ãã
å¯Ÿç §åç©ïŒãã175ngïŒïœãããããã·ãæäžå
ç©ãã«å¢å ããïŒïŒ°ïŒ0.001ïŒç¬¬ïŒè¡šïŒããã·ã³
ã®ã¿ã®æäžã¯è³å ã®MOPEGâSO4ã«å šã圱é¿ã
äžããªãã€ããããã®ã¢ããé žãçšããŠååŠçã
è¡ã€ãå Žåã«ã¯ãããããã·ãã«ããMOPEGâ
SO4ã®éã®å¢å 床ãäžå±€å€§ãããªããããªãã¡ã
175ngïŒKgïŒããããã·ãã®åç¬æäžãè¡ã€ãã©
ããã®å ŽåïŒãã203ngïŒïœã«å¢å ããïŒïŒ°ïŒ
0.01ïŒç¬¬è¡šïŒã
ãè¡šã
泚ïŒãããã®ïŒã€ã®å®éšã®åã
ã«ãããŠãïŒâ
ïŒå¹ã®ã©ãããïŒã°ã«ãŒãã«ããŠãåã°ã«ãŒãã®
ã©ããã«ãæå®ã®æäžéã®ããã·ã³ïŒè³å ã®ãã
ã®åæãä¿é²ããããšãç¥ãããŠããè¬å€ïŒ100
mgïŒKgãi.p.ïŒãããã¯ãã®åžéå€ã®ã¿ã泚å°ãã
ãããŠ30ååŸã«ããããã·ãïŒ400mgïŒKgãi.p.ïŒ
ãŸãã¯ãã®åžéå€ã®ã¿ã泚å°ããããã®ç¬¬ïŒåç®
ã®æ³šå°ãè¡ã€ãŠãã60ååŸã«è©Šéšåç©ã殺ããã
ã®è³å šäœã«ã€ããŠåæãè¡ã€ãŠããã·ã³ããã³
MOPEGâSO4ã®éã枬å®ãããããã·ã³ã®æäž
ã«ããè³å ã«ããã·ã³ã®éã¯èããå¢å ããïŒïŒ°
±0.001ïŒãäžæ¹ãããããã·ãã¯è³å ã®ããã·ã³
ãå€æ§ãããã®ã§ããªãããŸããå€æ¥ããã·ã³ãž
ã®ãã®ã¬ã¹ãã³ã¹ãå€æ¹ããããã®ã§ããªãã€
ããããããã·ãã¯è³å ã®MOPEGâSO4ã®éã
èããå¢å ããïŒïŒ°Â±0.001ïŒããããŠããã·ã³ã®
ååŠçã«ããããã®ã¬ã¹ãã³ã¹ãèããå¢å€§ãã
ïŒïŒ°Â±0.01ïŒããããã®å®éšããŒã¿ãŒã¯ãå€æ°äºå
解ææ³ã«ãã解æããããããã®å€ã¯ã±SENã
ã§è¡šããããã ã©ãããå¯å·ç°å¢ïŒïŒâïŒäžã«é£Œè²ããå Žåã«
ã¯ã€ã«ãšããããªã³ã®ã¿ãŒã³ãªãŒããŒéãå¢å
ãããããŠããã«ãã€ãŠãè³å ã®ãã€ãã³äžã®ã
ã«ãšããããªã³èªäœããã³ãã®ä»£è¬ç£ç©
ïŒMOPEGâSO4ïŒã®äž¡è ã®çæãä¿é²ãããã
ã©ãããå¯å·ç°å¢äžã«é£Œè²ããŠæ¬¡ã®ããšã調ã¹
ããããªãã¡ãè³å ã®ããã·ã³ã®éãå€ããåŠç
ã¯ãå¯å·ã¹ãã¬ã¹ãåããã©ããïŒããããã·ã
ãæäžããªãã€ãã©ããïŒã®è³å ã®MOPEGâ
SO4èç©é床ã«åœ±é¿ãäžãããã®ã§ãããã©ãã
ã調ã¹ãïŒç¬¬ïŒå³ïŒã å¯å·ç°å¢äžã«ïŒæé眮ããšè³å ã®MOPEGâ
SO4ã®éãçŽ40ïŒ å¢å ããïŒããªãã¡ãã®éã¯
80ngïŒïœãã114ngïŒïœã«å¢å ããïŒïŒ°ïŒ0.01ïŒã
ã¢ããé žãŸãã¯é£å¡©æ°Žã®ãããããæäžããè©Šéš
åç©ã§ã¯ãè³å ã®ããã·ã³ã®éã¯å€§äœåãã§ã
ãããã€ããã¯MOPEGâSO4ã®éã«å¯æ¥ã«é¢é£
ãããã®ã§ãã€ãïŒïœïŒ77ïŒïŒ°ïŒ0.05ïŒç¬¬ïŒå³ïŒã
ããã·ã³ã®æäžã«ããååŠçã«ããè³å ã®ããã·
ã³ã®éãçŽ80ïŒ å¢å ããããªãã¡ã13.3ÎŒïœïŒïœ
ïŒé£å¡©æ°Žã泚å°ããåç©ã®å ŽåïŒãã24.6ÎŒïœïŒïœ
ã«å¢å ããïŒïŒ°ïŒ0.01ããMOPEGâSO4ã®éã¯çŽ
70ïŒ å¢å ããïŒããªãã¡ã114nïœïŒïœãã193n
ïœïŒïœã«å¢å ããïŒïŒ°ïŒ0.01ïŒããã®å®éšã§ã¯ã
ãªã³ã®æäžã«ããååŠçãè¡ã€ããããã®å Žåã«
ã¯è³å ã®ããã·ã³ãŸãã¯MOPEGâSO4ã®éã¯å®
質çã«ç¡å€åã§ãã€ãïŒããªãã¡ãã®ïŒã€ã®éã¯
ãããã14.3ÎŒïœïŒïœããã³117nïœïŒïœã§ãã€
ãïŒãããããªãããä»ã®ã°ã«ãŒãã«å¯Ÿããå®éš
ã®çµæïŒç¬¬ïŒå³ïŒããæãããªããã«ãè³å ã®ã
ãã·ã³ããã³MOPEGâSO4ã®éã¯ãè©Šéšåç©èª
äœãšãå¯æ¥ã«é¢é£ãããã®ã§ãã€ãã 第ïŒå³èšèŒã®çžé¢é¢ä¿ã¯æ¬¡ã®å®éšã§åŸãããã
ã®ã§ãã€ãã è€æ°ã®ã°ã«ãŒãã®ã©ããã®åã ã®è ¹èå ã«ããª
ã³ïŒ200mgïŒKgïŒããŸãã¯è³å åžåæ§ã«é¢ããŠãã
ã·ã³ãšç«¶åããæ§è³ªãæããã¢ããé ž(8)ããŸãã¯
ããã·ã³ïŒãšãã«ãšã¹ãã«ã®åœ¢ã®ããã·ã³125
mgïŒKgïŒããŸãã¯é£å¡©æ°Žã泚å°ããã30ååŸã«ã
ã®ã©ãããã·ã³ã°ã«ã±ãŒãžïŒããïŒã«å ¥ããŠå¯å·
ç°å¢ïŒïŒâïŒäžã«çœ®ãããïŒæéåŸã«è©Šéšåç©ã
å šéšæ®ºãããã®è¡æ¶²å šéšã«ã€ããŠåæãè¡ã€ãŠã
ãã·ã³ããã³MOPEGâSO4ã®éã枬å®ããã察
ç §åç©ã«ã¯é£å¡©ã泚å°ããã·ã³ã°ã«ã±ãŒãžã«å ¥ã
ãŠå®€æž©ïŒ22âïŒã«ãããŠ90åéä¿ã€ããã°ã©ãäž
ã®åç¹ã¯ïŒã€ã®è³ã®äžã«ååšããããã·ã³ããã³
MOPEGâSO4ã®éãè¡šããããããã®ããŒã¿ãŒ
ã¯ãè¥å¹²ã®å®éšçµæãéèšããŠç®åºããããã®ã§
ãã€ãã宀枩ã«ãããŠé£Œè²ãããè©Šéšåç©ã®è³å
ã®ããã·ã³ããã³MOPEGâSO4ã®éã¯ãããã
14.6ÎŒïœããã³80nïœïŒïœã§ãã€ãã第ïŒå³ã®ã°ã©
ãã«ãããŠãåèšå·ã¯æ¬¡ã®æå³ãæããïŒé»äžžâŠ
ããªã³ã§ååŠçãããåç©ã«ããã枬å®å€ïŒçœäžž
âŠé£å¡©æ°Žã§ååŠçãããåç©ã«ããã枬å®å€ïŒçœ
ãåè§âŠããã·ã³ã§ååŠçãããåç©ã«ããã枬
å®å€ã è³å ã®ããã·ã³ã®éã®ççåŠçãã©ããããŸ
ãããã«ãšããããªã³ã®åæéããã³ã¿ãŒã³ãªãŒ
ããŒéïŒããã¯ãMOPEGâSO4ã®éã®æž¬å®ã«ã
ã枬å®ã§ããïŒã«åœ±é¿ãäžãããã®ã§ãããã©ã
ããã¿ãããã«ã次ã®å®éšãè¡ã€ããããªãã¡ã
å¯å·ç°å¢äžã«çœ®ããè©Šéšåç©ã«ãããäžèšã®ä»£è¬
ç£ç©ã®èç©éã調ã¹ãæäœããããã·ã³ã®éãé«
ãããšæãããåçŽé£ŒæïŒsingle mealïŒãé£ã¹
ãããåŸã«è¡ã€ãã ïŒæ©äžçµ¶é£ãããè©Šéšåç©ã«ç¡èçœé£ŒæïŒã«ãŒ
ã€ã³ïŒïŒ ïŒãŸãã¯40ïŒ ã«ãŒã€ã³é£Œæãåå10æã
ãåå11æãŸã§ã®æéã«ããã€ãŠäžãã次ãã§è©Š
éšåç©ãå¯å·ç°å¢ïŒïŒâïŒäžã«ïŒæéä¿ã¡ã次ã
ã§ããã殺ãããã®è³ãåæããŠããã·ã³ããã³
MOPEGâSO4ã®éã枬å®ããã絶é£ãããå¯Ÿç §
åç©ã¯ããã®ïŒæéã«ããã€ãŠå®€æž©ïŒ22âïŒã«ã
ããŠä¿ã€ãã 絶é£ãããã©ãããå¯å·ç°å¢äžã«ä¿ã€ããšã«ã
ãããã®è³å ã®MOPEGâSO4ã®èç©ãä¿é²ã§
ãããã®éã¯123nïœïŒ22âã«ãããŠä¿ããã絶
é£å¯Ÿç §åç©ïŒãã163nïœã«å¢å ããïŒïŒ°ïŒ0.05ïŒã
ãã®åŠçã¯è³å ã®ããã·ã³ã®éã«ã¯å šã圱é¿ãäž
ããªãã€ãïŒ10.1ÎŒïœïŒïœå¯Ÿ10.5ÎŒïœïŒïœïŒãå¯å·
ç°å¢äžã«çœ®ãããåç©ã®ãã¡ã§ãïŒïŒ ã«ãŒã€ã³é£Œ
æãŸãã¯40ïŒ ã«ãŒã€ã³é£Œæãæäžããåç©ã§ã¯ã
è³å ã®MOPEGâSO4ã®èç©éã40â50ïŒ å¢å ã
ãïŒç¬¬è¡šïŒïŒ°ïŒ0.01ïŒãïŒïŒ ã«ãŒã€ã³é£Œæãæ
äžããåç©ã§ã¯è³å ã®ããã·ã³ã®éãçŽ40ïŒ å¢å
ãïŒïŒ°ïŒ0.01ïŒãäžæ¹ã40ïŒ ã«ãŒã€ã³é£Œæãé£ã¹
ãåç©ã§ã¯è³å ã®ããã·ã³ã®éã77ïŒ å¢å ãã
ïŒïŒ°ïŒ0.01ïŒã ç¡èçœé£Œæã®æäžãè³å ã®ããã·ã³ã®éã®å¢å
ããããããªãã€ãå Žåã«ã¯ãè³å ã®MOPEGâ
SO4ã®éããŸãå¢å ããªãã€ãïŒç¬¬è¡šïŒããã®
å®éšã«ãããŠãèçœè³ªãæäžããåç©ã§ã¯è³å ã®
ããã·ã³éãçŽ50ïŒ å¢å ãïŒããªãã¡ã13.4ÎŒ
ïœïŒïœãã19.5ÎŒïœïŒïœã«å¢å ããïŒïŒ°ïŒ0.01ïŒã
ãã€ããã«äžŠè¡ããŠè³å ã®MOPEGâSO4ã®éã
å¢å ããã ãããã®å®éšããŒã¿ãŒããæãããªããã«ãã
ãããã·ãã§ååŠçããããŸãã¯å¯å·ç°å¢äžã«çœ®
ããã©ããã§ã¯ãè³å ã®ããã·ã³ã®éãå¢å ãã
ãåŠçãè¡ãããšã«ãããè³å ã®ãã«ãšããããª
ã³ã®ä»£è¬ç£ç©ã§ããMOPEGâSO4ã®èç©éãå¢
å ãããããšãã§ããã®ã§ããããã®ãããªåŠç
ã¯è¬çåŠçåŠçïŒããªãã¡ãããã·ã³ã®è ¹èå 泚
å°ïŒãŸãã¯ççåŠçåŠçïŒããªãã¡ãé«èçœè³ªé£Œ
æã®æäžïŒã§ãã€ãŠããããããã®åŠçã¯ãè³å
ã®ããã·ã³æ¿åºŠã«é¢ããŠããã®åºè³ªïŒãµãã¹ãã¬
ãŒãïŒã®ããã®ããã·ã³ããããã·ã©ãŒãŒã®é«Km
æ§ã«å¹æµããå¹æãäžãããã®ã§ããããã®é µçŽ
ã¯ãåºè³ªã«ã€ããŠå¶éæ¡ä»¶ããããšããæ¬ ç¹ãæ
ããããªããªãã°ããã®é µçŽ ã掻æ§åããããšã
ã«ããã®æŽ»æ§ãããã®ã³ãã¢ã¯ã¿ãŒã«å¯Ÿãã芪å
æ§ãéžæçã«é«ããããã§ããã MOPEGâSO4ã¯ã©ããã®è³å ã«ããããã«ãš
ããããªã³ã®äž»ä»£è¬ç£ç©ã§ãã€ãŠãããã¯ããã
ããã·ãã«ææãªã¡ã«ããºã ã«ããè³å€ã«éã³åº
ããããããããã·ãã®æäžåŸã«ã¯MOPEGâ
SO4ã¯ã©ããã®è³å ã«ãå°ãªããšã60åéã«ãã
ã€ãŠãæéã«çŽç·çã«æ¯äŸããéçå²åã§èç©ã
ãããã®æéã®éã¯è³å ã®ãã«ãšããããªã³ã®é
ã¯äžå€ç¶æ ã®ãŸãŸä¿ãããŠãããããMOPEGâ
SO4ã®èç©çïŒèç©éïŒã¯ããã«ãšããããªã³ã®
åæçã瀺ãæçšãªææšãšããŠåœ¹ç«ã€ãã®ã§ã
ãããã®èç©çã¯ãã¹ãã¬ã¹ãäžããã«ãããã
ã·ãåŠçãè¡ã€ãã©ããã®å Žåã«ã¯ãå¯å·ç°å¢äž
ã«çœ®ãããã©ããã®å Žåãããæããã«äœãã€ã
ïŒç¬¬è¡šããã³ç¬¬è¡šïŒãããããªãããã©ããã
ãã®ïŒã€ã®ç°å¢ã®ãã¡ã®ãããã®ç°å¢ã®ããšã§çœ®
ããå Žåã§ããäžèšã®èç©çã¯è³å ã®ããã·ã³ã®
éã«å·Šå³ãããå€ã§ããã
ïŒå¹ã®ã©ãããïŒã°ã«ãŒãã«ããŠãåã°ã«ãŒãã®
ã©ããã«ãæå®ã®æäžéã®ããã·ã³ïŒè³å ã®ãã
ã®åæãä¿é²ããããšãç¥ãããŠããè¬å€ïŒ100
mgïŒKgãi.p.ïŒãããã¯ãã®åžéå€ã®ã¿ã泚å°ãã
ãããŠ30ååŸã«ããããã·ãïŒ400mgïŒKgãi.p.ïŒ
ãŸãã¯ãã®åžéå€ã®ã¿ã泚å°ããããã®ç¬¬ïŒåç®
ã®æ³šå°ãè¡ã€ãŠãã60ååŸã«è©Šéšåç©ã殺ããã
ã®è³å šäœã«ã€ããŠåæãè¡ã€ãŠããã·ã³ããã³
MOPEGâSO4ã®éã枬å®ãããããã·ã³ã®æäž
ã«ããè³å ã«ããã·ã³ã®éã¯èããå¢å ããïŒïŒ°
±0.001ïŒãäžæ¹ãããããã·ãã¯è³å ã®ããã·ã³
ãå€æ§ãããã®ã§ããªãããŸããå€æ¥ããã·ã³ãž
ã®ãã®ã¬ã¹ãã³ã¹ãå€æ¹ããããã®ã§ããªãã€
ããããããã·ãã¯è³å ã®MOPEGâSO4ã®éã
èããå¢å ããïŒïŒ°Â±0.001ïŒããããŠããã·ã³ã®
ååŠçã«ããããã®ã¬ã¹ãã³ã¹ãèããå¢å€§ãã
ïŒïŒ°Â±0.01ïŒããããã®å®éšããŒã¿ãŒã¯ãå€æ°äºå
解ææ³ã«ãã解æããããããã®å€ã¯ã±SENã
ã§è¡šããããã ã©ãããå¯å·ç°å¢ïŒïŒâïŒäžã«é£Œè²ããå Žåã«
ã¯ã€ã«ãšããããªã³ã®ã¿ãŒã³ãªãŒããŒéãå¢å
ãããããŠããã«ãã€ãŠãè³å ã®ãã€ãã³äžã®ã
ã«ãšããããªã³èªäœããã³ãã®ä»£è¬ç£ç©
ïŒMOPEGâSO4ïŒã®äž¡è ã®çæãä¿é²ãããã
ã©ãããå¯å·ç°å¢äžã«é£Œè²ããŠæ¬¡ã®ããšã調ã¹
ããããªãã¡ãè³å ã®ããã·ã³ã®éãå€ããåŠç
ã¯ãå¯å·ã¹ãã¬ã¹ãåããã©ããïŒããããã·ã
ãæäžããªãã€ãã©ããïŒã®è³å ã®MOPEGâ
SO4èç©é床ã«åœ±é¿ãäžãããã®ã§ãããã©ãã
ã調ã¹ãïŒç¬¬ïŒå³ïŒã å¯å·ç°å¢äžã«ïŒæé眮ããšè³å ã®MOPEGâ
SO4ã®éãçŽ40ïŒ å¢å ããïŒããªãã¡ãã®éã¯
80ngïŒïœãã114ngïŒïœã«å¢å ããïŒïŒ°ïŒ0.01ïŒã
ã¢ããé žãŸãã¯é£å¡©æ°Žã®ãããããæäžããè©Šéš
åç©ã§ã¯ãè³å ã®ããã·ã³ã®éã¯å€§äœåãã§ã
ãããã€ããã¯MOPEGâSO4ã®éã«å¯æ¥ã«é¢é£
ãããã®ã§ãã€ãïŒïœïŒ77ïŒïŒ°ïŒ0.05ïŒç¬¬ïŒå³ïŒã
ããã·ã³ã®æäžã«ããååŠçã«ããè³å ã®ããã·
ã³ã®éãçŽ80ïŒ å¢å ããããªãã¡ã13.3ÎŒïœïŒïœ
ïŒé£å¡©æ°Žã泚å°ããåç©ã®å ŽåïŒãã24.6ÎŒïœïŒïœ
ã«å¢å ããïŒïŒ°ïŒ0.01ããMOPEGâSO4ã®éã¯çŽ
70ïŒ å¢å ããïŒããªãã¡ã114nïœïŒïœãã193n
ïœïŒïœã«å¢å ããïŒïŒ°ïŒ0.01ïŒããã®å®éšã§ã¯ã
ãªã³ã®æäžã«ããååŠçãè¡ã€ããããã®å Žåã«
ã¯è³å ã®ããã·ã³ãŸãã¯MOPEGâSO4ã®éã¯å®
質çã«ç¡å€åã§ãã€ãïŒããªãã¡ãã®ïŒã€ã®éã¯
ãããã14.3ÎŒïœïŒïœããã³117nïœïŒïœã§ãã€
ãïŒãããããªãããä»ã®ã°ã«ãŒãã«å¯Ÿããå®éš
ã®çµæïŒç¬¬ïŒå³ïŒããæãããªããã«ãè³å ã®ã
ãã·ã³ããã³MOPEGâSO4ã®éã¯ãè©Šéšåç©èª
äœãšãå¯æ¥ã«é¢é£ãããã®ã§ãã€ãã 第ïŒå³èšèŒã®çžé¢é¢ä¿ã¯æ¬¡ã®å®éšã§åŸãããã
ã®ã§ãã€ãã è€æ°ã®ã°ã«ãŒãã®ã©ããã®åã ã®è ¹èå ã«ããª
ã³ïŒ200mgïŒKgïŒããŸãã¯è³å åžåæ§ã«é¢ããŠãã
ã·ã³ãšç«¶åããæ§è³ªãæããã¢ããé ž(8)ããŸãã¯
ããã·ã³ïŒãšãã«ãšã¹ãã«ã®åœ¢ã®ããã·ã³125
mgïŒKgïŒããŸãã¯é£å¡©æ°Žã泚å°ããã30ååŸã«ã
ã®ã©ãããã·ã³ã°ã«ã±ãŒãžïŒããïŒã«å ¥ããŠå¯å·
ç°å¢ïŒïŒâïŒäžã«çœ®ãããïŒæéåŸã«è©Šéšåç©ã
å šéšæ®ºãããã®è¡æ¶²å šéšã«ã€ããŠåæãè¡ã€ãŠã
ãã·ã³ããã³MOPEGâSO4ã®éã枬å®ããã察
ç §åç©ã«ã¯é£å¡©ã泚å°ããã·ã³ã°ã«ã±ãŒãžã«å ¥ã
ãŠå®€æž©ïŒ22âïŒã«ãããŠ90åéä¿ã€ããã°ã©ãäž
ã®åç¹ã¯ïŒã€ã®è³ã®äžã«ååšããããã·ã³ããã³
MOPEGâSO4ã®éãè¡šããããããã®ããŒã¿ãŒ
ã¯ãè¥å¹²ã®å®éšçµæãéèšããŠç®åºããããã®ã§
ãã€ãã宀枩ã«ãããŠé£Œè²ãããè©Šéšåç©ã®è³å
ã®ããã·ã³ããã³MOPEGâSO4ã®éã¯ãããã
14.6ÎŒïœããã³80nïœïŒïœã§ãã€ãã第ïŒå³ã®ã°ã©
ãã«ãããŠãåèšå·ã¯æ¬¡ã®æå³ãæããïŒé»äžžâŠ
ããªã³ã§ååŠçãããåç©ã«ããã枬å®å€ïŒçœäžž
âŠé£å¡©æ°Žã§ååŠçãããåç©ã«ããã枬å®å€ïŒçœ
ãåè§âŠããã·ã³ã§ååŠçãããåç©ã«ããã枬
å®å€ã è³å ã®ããã·ã³ã®éã®ççåŠçãã©ããããŸ
ãããã«ãšããããªã³ã®åæéããã³ã¿ãŒã³ãªãŒ
ããŒéïŒããã¯ãMOPEGâSO4ã®éã®æž¬å®ã«ã
ã枬å®ã§ããïŒã«åœ±é¿ãäžãããã®ã§ãããã©ã
ããã¿ãããã«ã次ã®å®éšãè¡ã€ããããªãã¡ã
å¯å·ç°å¢äžã«çœ®ããè©Šéšåç©ã«ãããäžèšã®ä»£è¬
ç£ç©ã®èç©éã調ã¹ãæäœããããã·ã³ã®éãé«
ãããšæãããåçŽé£ŒæïŒsingle mealïŒãé£ã¹
ãããåŸã«è¡ã€ãã ïŒæ©äžçµ¶é£ãããè©Šéšåç©ã«ç¡èçœé£ŒæïŒã«ãŒ
ã€ã³ïŒïŒ ïŒãŸãã¯40ïŒ ã«ãŒã€ã³é£Œæãåå10æã
ãåå11æãŸã§ã®æéã«ããã€ãŠäžãã次ãã§è©Š
éšåç©ãå¯å·ç°å¢ïŒïŒâïŒäžã«ïŒæéä¿ã¡ã次ã
ã§ããã殺ãããã®è³ãåæããŠããã·ã³ããã³
MOPEGâSO4ã®éã枬å®ããã絶é£ãããå¯Ÿç §
åç©ã¯ããã®ïŒæéã«ããã€ãŠå®€æž©ïŒ22âïŒã«ã
ããŠä¿ã€ãã 絶é£ãããã©ãããå¯å·ç°å¢äžã«ä¿ã€ããšã«ã
ãããã®è³å ã®MOPEGâSO4ã®èç©ãä¿é²ã§
ãããã®éã¯123nïœïŒ22âã«ãããŠä¿ããã絶
é£å¯Ÿç §åç©ïŒãã163nïœã«å¢å ããïŒïŒ°ïŒ0.05ïŒã
ãã®åŠçã¯è³å ã®ããã·ã³ã®éã«ã¯å šã圱é¿ãäž
ããªãã€ãïŒ10.1ÎŒïœïŒïœå¯Ÿ10.5ÎŒïœïŒïœïŒãå¯å·
ç°å¢äžã«çœ®ãããåç©ã®ãã¡ã§ãïŒïŒ ã«ãŒã€ã³é£Œ
æãŸãã¯40ïŒ ã«ãŒã€ã³é£Œæãæäžããåç©ã§ã¯ã
è³å ã®MOPEGâSO4ã®èç©éã40â50ïŒ å¢å ã
ãïŒç¬¬è¡šïŒïŒ°ïŒ0.01ïŒãïŒïŒ ã«ãŒã€ã³é£Œæãæ
äžããåç©ã§ã¯è³å ã®ããã·ã³ã®éãçŽ40ïŒ å¢å
ãïŒïŒ°ïŒ0.01ïŒãäžæ¹ã40ïŒ ã«ãŒã€ã³é£Œæãé£ã¹
ãåç©ã§ã¯è³å ã®ããã·ã³ã®éã77ïŒ å¢å ãã
ïŒïŒ°ïŒ0.01ïŒã ç¡èçœé£Œæã®æäžãè³å ã®ããã·ã³ã®éã®å¢å
ããããããªãã€ãå Žåã«ã¯ãè³å ã®MOPEGâ
SO4ã®éããŸãå¢å ããªãã€ãïŒç¬¬è¡šïŒããã®
å®éšã«ãããŠãèçœè³ªãæäžããåç©ã§ã¯è³å ã®
ããã·ã³éãçŽ50ïŒ å¢å ãïŒããªãã¡ã13.4ÎŒ
ïœïŒïœãã19.5ÎŒïœïŒïœã«å¢å ããïŒïŒ°ïŒ0.01ïŒã
ãã€ããã«äžŠè¡ããŠè³å ã®MOPEGâSO4ã®éã
å¢å ããã ãããã®å®éšããŒã¿ãŒããæãããªããã«ãã
ãããã·ãã§ååŠçããããŸãã¯å¯å·ç°å¢äžã«çœ®
ããã©ããã§ã¯ãè³å ã®ããã·ã³ã®éãå¢å ãã
ãåŠçãè¡ãããšã«ãããè³å ã®ãã«ãšããããª
ã³ã®ä»£è¬ç£ç©ã§ããMOPEGâSO4ã®èç©éãå¢
å ãããããšãã§ããã®ã§ããããã®ãããªåŠç
ã¯è¬çåŠçåŠçïŒããªãã¡ãããã·ã³ã®è ¹èå 泚
å°ïŒãŸãã¯ççåŠçåŠçïŒããªãã¡ãé«èçœè³ªé£Œ
æã®æäžïŒã§ãã€ãŠããããããã®åŠçã¯ãè³å
ã®ããã·ã³æ¿åºŠã«é¢ããŠããã®åºè³ªïŒãµãã¹ãã¬
ãŒãïŒã®ããã®ããã·ã³ããããã·ã©ãŒãŒã®é«Km
æ§ã«å¹æµããå¹æãäžãããã®ã§ããããã®é µçŽ
ã¯ãåºè³ªã«ã€ããŠå¶éæ¡ä»¶ããããšããæ¬ ç¹ãæ
ããããªããªãã°ããã®é µçŽ ã掻æ§åããããšã
ã«ããã®æŽ»æ§ãããã®ã³ãã¢ã¯ã¿ãŒã«å¯Ÿãã芪å
æ§ãéžæçã«é«ããããã§ããã MOPEGâSO4ã¯ã©ããã®è³å ã«ããããã«ãš
ããããªã³ã®äž»ä»£è¬ç£ç©ã§ãã€ãŠãããã¯ããã
ããã·ãã«ææãªã¡ã«ããºã ã«ããè³å€ã«éã³åº
ããããããããã·ãã®æäžåŸã«ã¯MOPEGâ
SO4ã¯ã©ããã®è³å ã«ãå°ãªããšã60åéã«ãã
ã€ãŠãæéã«çŽç·çã«æ¯äŸããéçå²åã§èç©ã
ãããã®æéã®éã¯è³å ã®ãã«ãšããããªã³ã®é
ã¯äžå€ç¶æ ã®ãŸãŸä¿ãããŠãããããMOPEGâ
SO4ã®èç©çïŒèç©éïŒã¯ããã«ãšããããªã³ã®
åæçã瀺ãæçšãªææšãšããŠåœ¹ç«ã€ãã®ã§ã
ãããã®èç©çã¯ãã¹ãã¬ã¹ãäžããã«ãããã
ã·ãåŠçãè¡ã€ãã©ããã®å Žåã«ã¯ãå¯å·ç°å¢äž
ã«çœ®ãããã©ããã®å Žåãããæããã«äœãã€ã
ïŒç¬¬è¡šããã³ç¬¬è¡šïŒãããããªãããã©ããã
ãã®ïŒã€ã®ç°å¢ã®ãã¡ã®ãããã®ç°å¢ã®ããšã§çœ®
ããå Žåã§ããäžèšã®èç©çã¯è³å ã®ããã·ã³ã®
éã«å·Šå³ãããå€ã§ããã
ãè¡šã
ãè¡šã
äŸ
ãã®å®æœäŸã¯ãããã·ã³ã«ããåç©ã®è¡å§ãé
äžãããããšãäŸç€ºãããã®ã§ããã æ¬æ¥é«è¡å§ã§ããã©ããïŒSHâã©ããïŒïŒå
çš®ïŒãªã«ã¢ãïŒããã®å®éšã«çšããããã®ã©ãã
ã®äœéã¯280â320ïœã§ãããè¡å§ïŒå®éæïŒã¯
180â200mmHgã§ãã€ããè¡å§ã¯ãéæ¥çãªãã€
ã«ã«ãæ³ã«åŸã€ãŠãã«ã³ãã€ãªã·ã¹ãã ãããŠãŒ
ãããã¯ããã«ã¹ããã©ã³ã¹ãžãŠãŒãµãŒãçšããŠ
枬å®ãããå枬å®ã®å®æœåã«ã©ããã37âã«20å
éæããè¡å§ã¯ïŒå枬å®ãããã®å¹³åå€ãåã©ã
ãã«ã€ããŠåæç¹ã«ãããŠç®åºãããæäžâã¬ã¹
ãã³ã¹å®éšïŒç¬¬ïŒè¡šïŒã§ã¯ãåã°ã«ãŒãïŒïŒã°ã«
ãŒãã¯ïŒå¹ãããªãïŒã®ã©ããã®åºæºè¡å§ã枬å®
ããçŽåŸã«æå®éã®ããã·ã³ã¡ãã«ãšã¹ãã«ãè ¹
èå ã«æ³šå°ããïŒi.p.ïŒã1.5æéåŸã«ã©ããã®è¡
å§ãåã³æž¬å®ãããã®æž¬å®å€ããåºæºè¡å§ããã®
å€åéã®åœ¢ã§èšé²ãããããã·ã³âããªã³æäžå®
éšïŒç¬¬ïŒè¡šïŒã§ã¯ãåã°ã«ãŒãã®ã©ããïŒïŒã°ã«
ãŒãã¯ïŒå¹ãããªãïŒã®åºæºè¡å§ã枬å®ããåŸã«
æå®ã®æäžåŠçãè¡ã€ããå ¶åŸã«ïŒæéæ¯ã«è¡å§
ã枬å®ãããã®æž¬å®å€ãåºæºè¡å§ããã®å€åéãš
ããŠèšé²ããã ããã·ã³ã®æäžïŒããã·ã³ã¯ãäžå±€æº¶è§£åºŠã®å€§
ããæ°Žåã¡ãã«ãšã¹ãã«ã®åœ¢ã§äœ¿çšããïŒã«ã
ããè¡å§ãèããäœäžãããããã®äœäžã¯æäžé
ãšå¯æ¥ãªé¢é£æ§ãæãããã®ã§ãã€ãïŒç¬¬ïŒè¡šïŒã
æäžéã200â400mgïŒKgïŒããã¯çŽç²ãªããã·ã³
ã®æäžé156â312mgïŒKgã«çããïŒã§ãããšãã«
è¡å§äœäžéãæ倧å€ã«ãªã€ããããïŒã€ã®äžæ§ã¢
ãã³ã§ããããªã³ã®æäžæã«ã¯è¡å§ã¯å€åããªã
ã€ããïŒç¬¬ïŒè¡šïŒããããªããããã®æäžéïŒ100
mgïŒKgïŒã¯ãåœéå€ã®ããã·ã³ïŒãã®å®éšã§ã¯ã
çŽç²ãªè©²ã¢ããé žããªãã¡éé¢ç¶æ ã®è©²ã¢ããé ž
ãäžèšé䜿çšããïŒã®è¡å§éäžäœçšãå®å šã«é®æ
ããã ãããã®å®éšããŒã¿ãŒããæãããªããã«ãè³
å ã®ãšããããªã³ã®éãå¢å ã§ããããšãå€ã€ãŠ
ãããããªæäžéïŒäŸåç §ïŒã§ããã·ã³ãæäž
ããããšã«ãããé«è¡å§çã®åç©ã®è¡å§ãäºæ³é
ãã«äœäžãããããšãã§ããã®ã§ãããããïŒã€
ã®ç 究ã§ã¯ããã«ã¢ãã³ã·ãïŒnormotensiveïŒ
ãªã©ããã«ããã·ã³ïŒ100mgïŒKgïŒãæäžããã
ãšã«ãããè¡å§ãå°ãäœäžã§ãããããã®å Žåã®
äœäžéã¯ãé«è¡å§çã®å Žåã®äœäžéãããã¯ãã
ã«å°ãªãããšãèŠåºãããã
äžãããããšãäŸç€ºãããã®ã§ããã æ¬æ¥é«è¡å§ã§ããã©ããïŒSHâã©ããïŒïŒå
çš®ïŒãªã«ã¢ãïŒããã®å®éšã«çšããããã®ã©ãã
ã®äœéã¯280â320ïœã§ãããè¡å§ïŒå®éæïŒã¯
180â200mmHgã§ãã€ããè¡å§ã¯ãéæ¥çãªãã€
ã«ã«ãæ³ã«åŸã€ãŠãã«ã³ãã€ãªã·ã¹ãã ãããŠãŒ
ãããã¯ããã«ã¹ããã©ã³ã¹ãžãŠãŒãµãŒãçšããŠ
枬å®ãããå枬å®ã®å®æœåã«ã©ããã37âã«20å
éæããè¡å§ã¯ïŒå枬å®ãããã®å¹³åå€ãåã©ã
ãã«ã€ããŠåæç¹ã«ãããŠç®åºãããæäžâã¬ã¹
ãã³ã¹å®éšïŒç¬¬ïŒè¡šïŒã§ã¯ãåã°ã«ãŒãïŒïŒã°ã«
ãŒãã¯ïŒå¹ãããªãïŒã®ã©ããã®åºæºè¡å§ã枬å®
ããçŽåŸã«æå®éã®ããã·ã³ã¡ãã«ãšã¹ãã«ãè ¹
èå ã«æ³šå°ããïŒi.p.ïŒã1.5æéåŸã«ã©ããã®è¡
å§ãåã³æž¬å®ãããã®æž¬å®å€ããåºæºè¡å§ããã®
å€åéã®åœ¢ã§èšé²ãããããã·ã³âããªã³æäžå®
éšïŒç¬¬ïŒè¡šïŒã§ã¯ãåã°ã«ãŒãã®ã©ããïŒïŒã°ã«
ãŒãã¯ïŒå¹ãããªãïŒã®åºæºè¡å§ã枬å®ããåŸã«
æå®ã®æäžåŠçãè¡ã€ããå ¶åŸã«ïŒæéæ¯ã«è¡å§
ã枬å®ãããã®æž¬å®å€ãåºæºè¡å§ããã®å€åéãš
ããŠèšé²ããã ããã·ã³ã®æäžïŒããã·ã³ã¯ãäžå±€æº¶è§£åºŠã®å€§
ããæ°Žåã¡ãã«ãšã¹ãã«ã®åœ¢ã§äœ¿çšããïŒã«ã
ããè¡å§ãèããäœäžãããããã®äœäžã¯æäžé
ãšå¯æ¥ãªé¢é£æ§ãæãããã®ã§ãã€ãïŒç¬¬ïŒè¡šïŒã
æäžéã200â400mgïŒKgïŒããã¯çŽç²ãªããã·ã³
ã®æäžé156â312mgïŒKgã«çããïŒã§ãããšãã«
è¡å§äœäžéãæ倧å€ã«ãªã€ããããïŒã€ã®äžæ§ã¢
ãã³ã§ããããªã³ã®æäžæã«ã¯è¡å§ã¯å€åããªã
ã€ããïŒç¬¬ïŒè¡šïŒããããªããããã®æäžéïŒ100
mgïŒKgïŒã¯ãåœéå€ã®ããã·ã³ïŒãã®å®éšã§ã¯ã
çŽç²ãªè©²ã¢ããé žããªãã¡éé¢ç¶æ ã®è©²ã¢ããé ž
ãäžèšé䜿çšããïŒã®è¡å§éäžäœçšãå®å šã«é®æ
ããã ãããã®å®éšããŒã¿ãŒããæãããªããã«ãè³
å ã®ãšããããªã³ã®éãå¢å ã§ããããšãå€ã€ãŠ
ãããããªæäžéïŒäŸåç §ïŒã§ããã·ã³ãæäž
ããããšã«ãããé«è¡å§çã®åç©ã®è¡å§ãäºæ³é
ãã«äœäžãããããšãã§ããã®ã§ãããããïŒã€
ã®ç 究ã§ã¯ããã«ã¢ãã³ã·ãïŒnormotensiveïŒ
ãªã©ããã«ããã·ã³ïŒ100mgïŒKgïŒãæäžããã
ãšã«ãããè¡å§ãå°ãäœäžã§ãããããã®å Žåã®
äœäžéã¯ãé«è¡å§çã®å Žåã®äœäžéãããã¯ãã
ã«å°ãªãããšãèŠåºãããã
ãè¡šã
ãè¡šã
äŸ
ãã®å®æœäŸã¯ãããªãããã¢ã³ãé«è¡å§çã®å
ç©ã®è¡å§ãäžãããã®ã§ããããšãå ·äœäŸã«äŸç€º
ãããã®ã§ããã ããã§çšããããè©Šéšåç©ãåºæ¬çå®éšæ¡ä»¶ã
ãã³è¡å§æž¬å®æè¡ã¯äŸèšèŒã®ãã®ãšåãã§ãã€
ããè€æ°ã®ã°ã«ãŒãã®SHâã©ããïŒïŒã°ã«ãŒã
ã¯ïŒå¹ãããªãïŒã«ïŒ¬âããªãããã¢ã³ïŒéé¢å¡©
åºïŒã泚å°ããå ¶åŸã«ãæå®ã®æéééæ¯ã«è¡å§
ã枬å®ããã第衚èšèŒã®åŠããããªãããã¢ã³
ã125mgïŒKg泚å°ãããšãã«ã¯ãæäžåŸïŒæé以
å ã«è¡å§ã42mmHgäœäžããããã®çµæã¯ãå ¬ç¥
ã®ã»ãããã³ã¬ã»ãã¿ãŒæ®æç©è³ªïŒã¡ãã«ãŽãª
ã³ïŒïŒmgïŒKgïŒã®åæäŸäžã«ããé®æããããã
ã®ããšããæãããªããã«ãããªãããã¢ã³æäž
ã«ããèµ·ãè¡å§éäžã¯ãããªãããã¢ã³ãäŒéç©
質ãšããŠé垞䜿çšããè³ã®ãã€ãã³ã®äžã®ã»ãã
ãã³ã®åæéããã³ããããã®ãã®æŸåºéãå¢å
ããããã«èµ·ããã®ã§ãããšæãããã
ç©ã®è¡å§ãäžãããã®ã§ããããšãå ·äœäŸã«äŸç€º
ãããã®ã§ããã ããã§çšããããè©Šéšåç©ãåºæ¬çå®éšæ¡ä»¶ã
ãã³è¡å§æž¬å®æè¡ã¯äŸèšèŒã®ãã®ãšåãã§ãã€
ããè€æ°ã®ã°ã«ãŒãã®SHâã©ããïŒïŒã°ã«ãŒã
ã¯ïŒå¹ãããªãïŒã«ïŒ¬âããªãããã¢ã³ïŒéé¢å¡©
åºïŒã泚å°ããå ¶åŸã«ãæå®ã®æéééæ¯ã«è¡å§
ã枬å®ããã第衚èšèŒã®åŠããããªãããã¢ã³
ã125mgïŒKg泚å°ãããšãã«ã¯ãæäžåŸïŒæé以
å ã«è¡å§ã42mmHgäœäžããããã®çµæã¯ãå ¬ç¥
ã®ã»ãããã³ã¬ã»ãã¿ãŒæ®æç©è³ªïŒã¡ãã«ãŽãª
ã³ïŒïŒmgïŒKgïŒã®åæäŸäžã«ããé®æããããã
ã®ããšããæãããªããã«ãããªãããã¢ã³æäž
ã«ããèµ·ãè¡å§éäžã¯ãããªãããã¢ã³ãäŒéç©
質ãšããŠé垞䜿çšããè³ã®ãã€ãã³ã®äžã®ã»ãã
ãã³ã®åæéããã³ããããã®ãã®æŸåºéãå¢å
ããããã«èµ·ããã®ã§ãããšæãããã
ãè¡šã
ïŒã¡ãã«ãŽãªã³
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ è¡å§éäžå€çµæç©ã«ãããŠãããªãããã¢ã³
ããè¡å§éäžã®ããã«æå¹ãªéå«æããããšãç¹
城ãšããçµæç©ã ïŒ ç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®çµæç©ã«ãã
ãŠã (a) ããªãããã¢ã³ãšã (b) ãã¢ãžããžãŠã¬ããã¯ã11ã17αâãžã¡ãã
ã·â18βâïŒïŒïŒïŒïŒâããªã¡ããã·ãã³ãŸ
ã€ã«ãªãã·ïŒœâ3βïŒ20αâãšãã³ãã³â16βâã«
ã«ãã³é žã¡ãã«ãšã¹ãã«ãαâã¡ãã«ãããã
ãã©ã«ã¢ãžã³ãã°ã¢ãããžã³ãããšããã·ãã³
ãºã¢ãããïŒâïŒïŒïŒïŒâãžã¯ããããšãã«ã¢
ããïŒâïŒâã€ãããŸãªã³ãã€ããã¯ãã©ã€ãã
ãããã©ãããŒã«ãããã»ããããšã¿ã¯ãªãã
ã¯é žãã¹ãããã©ã¯ãã³ããŸãã¯è¬çåŠçã«èš±
容ããåŸããããã®å¡©ãããã³ãããã®æ··åç©
ãããªã矀ããéžæãããè¡å§éäžæå¹éã®è¡
å§éäžå€ ãšãå«æãããããŠæå(a)ã®æäžéãïŒâ100
mgïŒKgïŒäœéïŒã§ããããšãç¹åŸŽãšããçµæç©ã
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89874078A | 1978-04-24 | 1978-04-24 | |
| US05/963,857 US4296119A (en) | 1978-04-24 | 1978-11-27 | Process and composition for reducing blood pressure in animals |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS54145220A JPS54145220A (en) | 1979-11-13 |
| JPH0138087B2 true JPH0138087B2 (ja) | 1989-08-11 |
Family
ID=27129213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4983179A Granted JPS54145220A (en) | 1978-04-24 | 1979-04-24 | Blood pressure lowering composition |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4296119A (ja) |
| EP (1) | EP0005057A1 (ja) |
| JP (1) | JPS54145220A (ja) |
| CA (1) | CA1119956A (ja) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE30210T1 (de) * | 1981-07-15 | 1987-10-15 | Richard J Wurtman | Zusammensetzung zur erhoehung des blutdrucks. |
| US4542123A (en) * | 1982-01-11 | 1985-09-17 | Massachusetts Institute Of Technology | Composition and method for increasing brain tyrosine levels |
| CA1204666A (en) * | 1982-03-08 | 1986-05-20 | Richard J. Wurtman | Method for improving sleep |
| IT1148618B (it) * | 1982-10-11 | 1986-12-03 | Polifarma Spa | Procedimento enzimatico per la produzione di acido 3-indolpiruvico e utilizzazione farmaceutica di questo |
| ATE45672T1 (de) * | 1983-05-16 | 1989-09-15 | Massachusetts Inst Technology | Eine pharmazeutische zusammensetzung zum zweck der behandlung einer neurologischen krankheit oder des alterns. |
| WO1989002737A1 (en) * | 1987-09-30 | 1989-04-06 | University Of Florida | Treatment of hypertension by chronic administration of l-tryptophan or l-5-hydroxytryptophan |
| WO1991001724A1 (en) * | 1989-07-27 | 1991-02-21 | G.D. Searle & Co. | Renal-selective prodrugs for the treatment of hypertension |
| WO1992001667A1 (en) * | 1990-07-25 | 1992-02-06 | G.D. Searle & Co. | Renal-selective prodrugs for control of renal sympathetic nerve activity in the treatment of hypertension |
| US5393784A (en) * | 1993-07-21 | 1995-02-28 | New York State Office Of Mental Health | Treatment of tardive dyskinesia with leucine, isoleucine, valine or mixtures thereof |
| US5670539A (en) * | 1993-07-21 | 1997-09-23 | New York State Office Of Mental Health | Treatment of movement disorders using large neutral amino acids |
| US6369114B1 (en) | 1999-11-30 | 2002-04-09 | Institute Of Critical Care Medicine | Administration of an α2-adrenergic receptor agonist to enhance cardiopulmonary resuscitation |
| WO2004024188A1 (ja) * | 2002-09-12 | 2004-03-25 | Nihon Medi-Physics Co., Ltd. | è¬ç©ã®è¡æŒ¿èçœè³ªçµåãå¶åŸ¡ããããã®è£œå€ |
| JP3981042B2 (ja) * | 2003-06-09 | 2007-09-26 | ã¢ã«ãã¹é»æ°æ ªåŒäŒç€Ÿ | ã³ã³ã¿ã¯ããããŒãåã³ãããŒããœã±ããåã³é»æ°ç¹æ§æž¬å®è£ 眮䞊ã³ã«ã³ã³ã¿ã¯ããããŒãã®æŒãåœãŠæ¹æ³ |
| JP4605631B2 (ja) * | 2004-01-23 | 2011-01-05 | ã«ã«ãã¹æ ªåŒäŒç€Ÿ | ã¢ã³ãžãªãã³ã·ã³å€æé µçŽ é»å®³å€ |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3362879A (en) * | 1965-01-11 | 1968-01-09 | Health Education Welfare Usa | Tyrosine tranquilizing compositions and methods of treatment |
| US3360434A (en) * | 1965-03-22 | 1967-12-26 | Udenfriend Sidney | Method for reducing blood pressure with phenylalanine derivatives |
-
1978
- 1978-11-27 US US05/963,857 patent/US4296119A/en not_active Expired - Lifetime
-
1979
- 1979-04-20 EP EP79300649A patent/EP0005057A1/en not_active Withdrawn
- 1979-04-24 JP JP4983179A patent/JPS54145220A/ja active Granted
- 1979-04-24 CA CA000326254A patent/CA1119956A/en not_active Expired
Non-Patent Citations (1)
| Title |
|---|
| CHEM ABSTR * |
Also Published As
| Publication number | Publication date |
|---|---|
| CA1119956A (en) | 1982-03-16 |
| JPS54145220A (en) | 1979-11-13 |
| EP0005057A1 (en) | 1979-10-31 |
| US4296119A (en) | 1981-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6110973A (en) | Methods for treating obesity and weight gain using optically pure (-)-bupropion | |
| JPH0138087B2 (ja) | ||
| Murphy | Dopamine: a role in the pathogenesis and treatment of hypertension | |
| JP2001503737A (ja) | ç³å°¿ç ã®çºçãé²æ¢ããããã®ã·ããã©ãã³é¡äŒŒäœã®å©çš | |
| JP2022537878A (ja) | ã¢ãã¬ãã©ã¹ãããã³ïœïœïœïŒé»å®³å€ãå«ã䜵çšçæ³ | |
| CA2318960A1 (en) | Pharmaceutical uses of optically pure (+)-bupropion | |
| US20050054652A1 (en) | Methods of treating metabolic syndrome using dopamine receptor agonists | |
| WO1999053956A1 (en) | Remedies for obesity | |
| EP1539153A2 (en) | Therapeutic treatment for the metabolic syndrome and type 2 diabetes | |
| US4397866A (en) | Process for increasing glycine levels in the brain and spinal cord | |
| JPS647044B2 (ja) | ||
| US20040220190A1 (en) | Methods of treating metabolic syndrome using dopamine receptor agonists | |
| US7915262B2 (en) | Combination preparations comprising SLV308 and a dopamine agonist | |
| US4405629A (en) | Process for increasing glycine levels in the brain and spinal cord | |
| EP0005333B1 (en) | A pharmaceutical composition comprising an amino acid for reducing blood serum prolactin levels | |
| DK171392B1 (da) | Anvendelse af N-(2-hydroxyethyl)nicotinamidnitrat eller et farmaceutisk acceptabelt salt deraf til fremstilling af et farmaceutisk prÊparat til forÞgelse af hjernens glucoseoptagelse | |
| US4224343A (en) | Process and composition for decreasing blood serum prolactin levels | |
| US20250161270A1 (en) | Pharmaceutical composition and medicament comprising l-tryptophan, l-5-hydroxytryptophan and a peripheral degradation inhibitor | |
| CA1156148A (en) | Process for reducing depression | |
| HK40123243A (zh) | çšçæ°šé žèœ¬è¿æå¶åæ²»çèæ§ååççç»åç©åæ¹æ³ | |
| JPH03376B2 (ja) | ||
| HK1141464A (en) | Droxidopa and pharmaceutical composition thereof for the treatment of fibromyalgia | |
| HK1135017A (en) | Combination preparations comprising slv308 and a l-dopa | |
| MX2008016225A (es) | Preparaciones de combinacion que comprenden slv308 y l-dopa. |