Seeman P, Van Tol H H
Department of Pharmacology, University of Toronto, Ontario, Canada.
Trends Pharmacol Sci. 1994 Jul;15(7):264-70. doi: 10.1016/0165-6147(94)90323-9.
Dopamine receptors are the primary targets in the treatment of schizophrenia, Parkinson's disease, and Huntington's chorea, and are discussed in this review by Philip Seeman and Hubert Van Tol. Improved therapy may be obtained by drugs that selectively target a particular subtype of dopamine receptor. Most antipsychotic drugs block D2 receptors in direct correlation to clinical potency, except clozapine, which prefers D4 receptors. D1 and D2 receptors can enhance each other's actions, possibly through subunits of the G proteins. In schizophrenia, the D2 and D3 receptor density is elevated by 10%, while the D4 receptor density is elevated by 600%. Therefore, D4 receptors may be a target for future antipsychotic drugs. While antipsychotics originally helped to discover dopamine receptors, the five cloned dopamine receptors are now facilitating the discovery of selective antipsychotic and antiparkinson drugs.
多巴胺受体是治疗精神分裂症、帕金森病和亨廷顿舞蹈症的主要靶点，菲利普·西曼和休伯特·范·托尔在本综述中对其进行了讨论。通过选择性靶向特定亚型多巴胺受体的药物可能会获得更好的治疗效果。除了更倾向于作用于D4受体的氯氮平外，大多数抗精神病药物阻断D2受体的能力与临床效力直接相关。D1和D2受体可能通过G蛋白亚基相互增强作用。在精神分裂症中，D2和D3受体密度升高了10%，而D4受体密度升高了600%。因此，D4受体可能是未来抗精神病药物的靶点。虽然抗精神病药物最初有助于发现多巴胺受体，但现在五个克隆的多巴胺受体正推动着选择性抗精神病药物和抗帕金森药物的发现。
