DOPAMINE RECEPTORS, ANTIPSYCHOTIC DRUGS & SCHIZOPHRENIA

抗精神病药物被假设发挥其临床作用， 通过直接阻断脑和垂体多巴胺的作用 受体。 现在很清楚，多巴胺的多种亚型 受体存在，D1和D2，它们对 抗精神病药物 D1和D2多巴胺受体均介导 动物的行为反应。 多巴胺受体会 通过计算机分析的放射性配体结合进行体外表征 技术与多巴胺能3 H-配体，并通过研究 多巴胺敏感性腺苷酸环化酶（刺激性和 抑制的）。 生物化学和药理学特征 这些系统中的哪一个群体的多巴胺 每个人都可以识别。 这将由以下人员确认： 病变研究、功能研究和对修改的反应 膜环境和受体结构 试剂 这些研究将确定潜在的自身受体，前- 和突触后多巴胺受体亚型，并详细介绍了一些 区分激动剂形式的分子机制 拮抗剂受体相互作用和转导腺苷酸 环化酶调节 这些受体参数将是 在对照患者的死后大脑中进行了研究， 精神分裂症患者 失神经支配引起的多巴胺受体活性降低，或 抗精神病药物的慢性阻滞导致行为 伴随着受体数量增加的超敏反应。 这种药物诱导的多巴胺受体的增加已经被证实是 假设是迟发性运动障碍的病因。 响应 多巴胺受体亚型对去神经支配或慢性阻滞的反应 亚型选择性和非选择性抗精神病药物的使用 研究以确定参与的分子机制， 受体结合增加或调节过程发生变化。 用激动剂进行慢性刺激的效果也将被证实。 研究了 将评价多巴胺受体周转率 利用一种新的技术。 受体放射自显影将是 来确定多巴胺的解剖位置 受体亚型以及它们是否表现出差异 对上述操作的反应。 不同脑群的生化特征 多巴胺受体为开发新的 多巴胺能激动剂和拮抗剂的种类， 特异性治疗作用和降低的副作用发生率。

Antipsychotic drugs are hypothesized to exert their clinical effects through direct blockade of brain and pituitary dopamine receptors. It is now clear that multiple subtypes of dopamine receptors exist, D1 and D2, which have differential affinities for antipsychotic drugs. Both D1 and D2 dopamine receptors mediate behavioral responses in animals. Dopamine receptors will be characterized in vitro by computer-analyzed radioligand binding techniques with dopaminergic 3H-ligands, and by studies of dopamine-sensitive adenylate cyclases (both stimulatory and inhibitory). The biochemical and pharmacological characteristics of these systems will suggest which populations of dopamine receptors that each may identify. This will be confirmed by lesion studies, functional studies, and response to modification of membrane environment and receptor structure with specific reagents. Such studies will identify potential autoreceptors, pre- and post-synaptic dopamine receptor subtypes and detail some of the molecular mechanisms which differentiate agonist form antagonist receptor interaction and transduction to adenylate cyclase regulation. These receptor parameters will be investigated within postmortem brains from control patients and patients with schizophrenia. Decreased dopamine receptor activity caused by denervation or chronic blockade with antipsychotic drugs results in behavioral supersensitivity accompanied by an increase in receptor number. Such drug-induced increases in dopamine receptors have been hypothesized to be etiologic in tardive dyskinesia. The response of dopamine receptor subtypes to denervation or chronic blockade with subtype-selective and nonselective antipsychotics will be investigated to determine the molecular mechanisms involved in increased receptor binding or changes in regulatory processes. The effects of chronic stimulation with agonists will also be investigated. Dopamine receptor turnover will be evaluated utilizing a novel technique. Receptor autoradiography will be performed to determine the anatomical location of dopamine receptor subtypes and whether they demonstrate differential responses to the above manipulations. The biochemical characterization of distinct populations of brain dopamine receptors holds promise for the development of new classes of dopaminergic agonists and antagonists with more specific therapeutic action and lowered incidence of side-effects.