| Project/Area Number |
60480264
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Shinshu University (1986)
国立武蔵療養所 (1985) |
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Principal Investigator |
TORU Michio Professor, Department of Psychiatry, Shinshu University, School of Medicine, 医学部, 教授 (20013972)
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| Co-Investigator(Kenkyū-buntansha) |
HATA Norio Assistant, Department of Psychiatry, Shinshu University, School of Medicine, 医学部, 助手 (80189547)
SHIMIZU Hiromitsu Assistant, Department of Psychiatry, Shinshu University, School of Medicine, 医学部, 助手 (70178987)
OGATA Hiroshi Associate professor, Department of Psychiatry, Shinshu University, School of Med, 医学部, 助教授 (30020861)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1986: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1985: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Antipsychotic drugs / Antidepressant drugs / Antiparkinsonian drugs / Dopamine <D_2> receptor / Adrenaline <(alpha)_1> receptor / Adrenaline <(alpha)_2> receptor / Muscarinic cholinergic receptor / セロトニン【S_2】受容体 |
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| Research Abstract |
The inhibition of dopamine <D_2> , adrenaline <(alpha)_1> , <(alpha)_2> , muscarinic cholinergic and serotonin <S_2> receptor binding to human brain by various psychotropic drugs was studied. <^3H> -Spiperone and putamen was used for <D_2> , <^3H> -WB4101 and cerebral cortex for <(alpha)_1> , <^3H> -idazoxan and cerebral cortex for <(alpha)_2> , <^3H> -quinuclidinyl benzilate and cerebral cortex for muscarinic cholinergic and <^3H> -spiperone and cerebral cortex for <S_2> receptor binding. The <D_2> receptor binding was most strongly inhibited by butyrophenones, and then phenothiazines. There were some antidepressants which inhibited <D_2> receptor binding as strong as antipsychotic drugs. <(alpha)_1> Receptor inhibition of phenothiazines was generally stronger than butyrophenones. This fact will explain that antinoradrenergic <(alpha)_1> side effects such as sedation or orthostatic hypotension were observed more in patients on phenothiazine medication. The most potent anticholinergic
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drugs were antiparkinsonian drugs, then antidepressants, and then antipsychotic drugs. Anticholinergic effects of phenothiazines were much stronger than the other antipsychotic drugs. Anticholinergic activity of nontricyclic antidepressants was found to be weaker than conventional tricyclics. Mianserin most potently inhibited both <(alpha)_2> and <S_2> receptor binding. All the psychotropic drugs tested, including antipsychotic, antiparkinsonian and antidepressant drugs except mianserin, showed almost same weak inhibition of spicific <^3H> -idazoxan binding with <IC_(50)> values of approximately <10^(-6)> M. Among the antipsychotics, timiperone inhibited <S_2> receptor most strongly with <IC_(50)> value of 6.25 x <10^(-6)> M. The mechanism of antidepressant action of mianserin may be explained by the hypothesis that mianserin inhibits the presynaptic <(alpha)_2> receptors so that the release of noradrenaline increases. Since ritanserin, a selective <S_2> antagonist, is reported to be effective on depressive symptoms, it is possible to explain that the action of mianserin is due to its potent inhibition of <S_2> receptors. Less
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