Studies on action mechanisms of psychotropic drugs

精神药物作用机制研究

• 批准号: 60480264
• 负责人: TORU Michio
• 金额: $ 4.22万
• 依托单位: Shinshu University (1986)国立武蔵療養所 (1985)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60480264/
• 关键词: 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

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 … More 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

研究了各种精神药物对多巴胺< d2 >、肾上腺素<(α)_1>、<(α)_2>、毒蕈碱胆碱能和血清素<S_2>受体与人脑结合的抑制作用。< d2 >用< 3H> -WB4101与大脑皮层结合，< 3H> -吡唑嗪与大脑皮层结合<(α)_2>, < 3H> -苯磺酸醌与大脑皮层结合毒蕈碱胆碱能，< 3H> -Spiperone与大脑皮层结合<S_2>受体。<D_2>受体结合受丁苯酮抑制最强烈，其次是吩噻嗪类。部分抗抑郁药对<D_2>受体结合的抑制作用与抗精神病药相当。吩噻嗪类药物对<(α)_1>受体的抑制作用普遍强于丁苯酮类药物。这一事实将解释为什么抗肾上腺素能<(α)_1>的副作用，如镇静或体位性低血压在服用吩噻嗪的患者中观察到更多。最有效的抗胆碱能药…更多的是抗帕金森病药，然后是抗抑郁药，然后是抗精神病药。吩噻嗪类药物的抗胆碱能作用明显强于其他抗精神病药物。非三环类抗抑郁药的抗胆碱能活性弱于常规三环类药物。眠色林对<(α)_2>和<S_2>受体结合的抑制作用最强。除米安色林外，所有精神药物（包括抗精神病药、抗帕金森药和抗抑郁药）对<^3H> -咪唑嗪结合的特异性抑制作用几乎相同，<IC_(50)>值约为<10^(-6)> m。米安色林对<S_2>受体抑制作用最强，<IC_(50)>值为6.25 × <10^(-6)> m。米安色林抗抑郁作用的机制可能是通过抑制突触前<(α)_2>受体，使去甲肾上腺素的释放增加。由于利坦色林是一种选择性<S_2>拮抗剂，据报道对抑郁症状有效，因此可以解释米安色林的作用是由于其对<S_2>受体的有效抑制。少

项目成果

融道男ほか: 臨床精神医学. 15. 1475-1486 (1986)

Michio Yu 等人：临床精神病学 15. 1475-1486 (1986)

融道男: 神経研究の進歩. 30. 721-735 (1986)

余道雄：神经学研究进展 30. 721-735 (1986)

融道男: 精神神経薬理シンポジウム. 12. 57-61 (1986)

余道雄：精神神经药理学研讨会。12. 57-61 (1986)

融道男: 精神科治療学. 1. 60-66 (1986)

余道雄：精神病治疗学 1. 60-66 (1986)

融道男: Neurosurgeons. 5. 175-178 (1986)

余道雄：神经外科医生。5. 175-178 (1986)