DOPAMINE RECEPTORS, ANTIPSYCHOTIC DRUGS & SCHIZOPHRENIA

抗精神病药物被假设为在临床上发挥其作用 直接阻断大脑和垂体多巴胺的作用 感受器。现在很明显，多个亚型的多巴胺 存在受体d1和d2，它们对 抗精神病药物。D_1和D_2多巴胺受体均介导 动物的行为反应。多巴胺受体将是 计算机分析放射性配基结合的体外特征 技术与多巴胺能~3H配体，并通过研究 多巴胺敏感的腺苷酸环化酶(刺激性和 抑制性)。生物化学和药理特性 这些系统中的哪一组会提示多巴胺 每一个都可以识别的受体。这将由以下人员确认 损伤研究、功能研究和对修饰的反应 膜环境和受体结构与特异性 试剂。这类研究将识别潜在的自体受体，前 和突触后多巴胺受体亚型，并详细介绍了 区分激动剂形态的分子机制 拮抗剂受体相互作用与腺苷转导 环化酶调节。这些受体参数将是 在对照组和对照组的死后脑内进行调查 精神分裂症患者。 去神经或其他原因引起的多巴胺受体活性降低 抗精神病药物的长期阻断导致行为 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增加是 推测是迟发性运动障碍的病因。他们的回应 多巴胺受体亚型到失神经或慢性阻断 具有亚型选择性和非选择性的抗精神病药物 研究以确定涉及到的分子机制 受体结合增加或调节过程发生变化。 使用激动剂的慢性刺激的效果也将是 调查过了。将评估多巴胺受体的周转 利用一种新技术。受体放射自显影将是 以确定多巴胺的解剖位置 受体亚型及其是否表现出差异性 对上述操纵的反应。 不同脑群的生化特征 多巴胺受体有望开发新的 多巴胺能激动剂和拮抗剂的类别 疗效确切，副作用发生率低。

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.