Studies on action mechanisms of psychotropic drugs

精神药物作用机制研究

基本信息

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

项目摘要

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<^3H>-Spiperone和壳核对多巴胺<D_2>、肾上腺素<(alpha)_1>、<(alpha)_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。用于 <D_2> 、 <^3H> -WB4101 和大脑皮层<(alpha)_1> 、 <^3H> - 咪唑克生和大脑皮层 <(alpha)_2> 、 <^3H> - 奎宁环苯甲酸和大脑皮层毒蕈碱胆碱能和 <^3H> - 螺哌隆和大脑皮层 <S_2 > 受体结合。丁酰苯类对<D_2>受体结合的抑制最为强烈，其次是吩噻嗪类。抑制 <D_2> 受体结合的抗抑郁药与抗精神病药一样强。吩噻嗪类药物的受体抑制作用通常强于丁酰苯，这一事实可以解释抗去甲肾上腺素能 <(alpha)_1> 的副作用，例如镇静或体位性低血压。在服用吩噻嗪药物的患者中观察到更多，最有效的抗胆碱能药物是抗帕金森病药物。抗抑郁药，然后是抗精神病药，吩噻嗪的抗胆碱能作用比其他抗精神病药强得多，发现非三环类抗抑郁药的抗胆碱能活性弱于传统的三环类药物。所有测试的精神药物，包括抗精神病药、抗帕金森病药和抗抑郁药（米安色林除外）均显示出结合。对特异性 <^3H> -咪唑克生结合的抑制几乎相同，<IC_(50)> 值约为 <10^(-6)> M。在抗精神病药中，替米哌隆对 <S_2> 受体的抑制作用最强，<IC_(50)> 值约为 <10^(-6)> M。 (50 )> 值为 6.25 x <10^(-6)> M。米安色林的抗抑郁作用机制可以通过米安色林抑制的假设来解释突触前 <(alpha)_2> 受体，从而增加去甲肾上腺素的释放。据报道，利坦色林（一种选择性 <S_2> 拮抗剂）对抑郁症状有效，因此可以解释米安色林的作用是由于其作用。对<S_2>受体的有效抑制作用较小。