Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains
Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains
复制标题
3H-精神安定药和 3H-阿扑吗啡在精神分裂症患者大脑中的结合
作者：
Tyrone Lee;P. Seeman;W. Tourtellotte;I. Farley;Oleh Hornykeiwicz
19521 年推出的抗精神病药物或抗精神病药物可有效预防精神分裂症患者的复发和再住院。这些药物为定位精神分裂症患者大脑中可能存在的异常提供了一种策略。精神分裂症可能与异常敏感的多巴胺突触有关 3-6 的假说是从抗精神病药阻断多巴胺受体从而加速多巴胺周转的建议演变而来的7,8。该假说还得到了以下观察结果的支持：多巴胺模拟药物（例如 d-安非他明、左旋多巴）会引起或加剧精神病症状 9-12，抗精神病药对多巴胺产生超敏反应 13-15，阻断儿茶酚胺合成的药物会增强抗精神病药和抗精神病作用 16，抗精神病药都具有与多巴胺相匹配的构象 17，多巴胺是抑制 3H-氟哌啶醇与大脑富含多巴胺区域的特异性结合的最有效的神经递质18-20。尽管精神分裂症多巴胺假说的所有这些证据都是间接的，但我们现在通过测量 3H-阿朴吗啡和 3H-氟哌啶醇或 3H-螺哌酮与精神分裂症患者死后大脑四个区域的特异性结合，获得了精神分裂症大脑多巴胺受体某些异常的直接证据。
THE neuroleptic or antipsychotic drugs, introduced in 19521, effectively prevent relapse and rehospitalisation of schizophrenic patients. These drugs provide a strategy2 for localising possible abnormalities in the brain in schizophrenia. The hypothesis that schizophrenia might be associated with abnormally sensitive dopamine synapses3–6 evolved from the suggestion that neuroleptics block dopamine receptors and thus accelerate the turnover of dopamine7,8. The hypothesis received additional support from the observations that dopamine-mimetic drugs (for example d-amphetamine, L-dopa) elicit or exacerbate psychotic symptoms9–12, that neuroleptics produce supersensitivity to dopamine13–15, that the neuroleptic and antipsychotic actions are enhanced by drugs which block the synthesis of catecholamines16, that neuroleptics all have conformations that match that of dopamine17, and that dopamine is the most potent neurotransmitter to inhibit the specific binding of 3H-haloperidol to dopamine-rich regions of the brain18–20. Although all this evidence for the dopamine hypothesis of schizophrenia is circumstantial, we have now obtained direct evidence for some abnormalities in brain dopamine receptors in schizophrenia by measuring the specific binding of 3H-apomorphine and 3H-haloperidol or 3H-spiperone to four regions of postmortem brains from schizophrenic patients.