Stone J M, Pilowsky L S
Section of Neurochemical Imaging, Kings College London Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK.
CNS Neurol Disord Drug Targets. 2007 Aug;6(4):265-72. doi: 10.2174/187152707781387323.
Since the discovery of the first antipsychotic drug, chlorpromazine, in the early 1950s, all effective antipsychotic drugs have been found to share the common property of dopamine D2 receptor antagonism. There has been some suggestion that simple D2 receptor antagonism may not confer optimal antipsychotic efficacy. Currently available antipsychotic drugs leave many symptoms of the illness untreated and cause unacceptable side effects. Recent research in schizophrenia suggests a number of potential new non-D2 targets for pharmacotherapy including glutamate, acetylcholine and serotonin neurotransmitter systems. This review summarises the main neurochemical theories of schizophrenia, and, in the light of these, examines possible therapeutic targets for new antipsychotic drugs.
自20世纪50年代初发现第一种抗精神病药物氯丙嗪以来,所有有效的抗精神病药物都被发现具有多巴胺D2受体拮抗的共同特性。有人提出,单纯的D2受体拮抗作用可能无法带来最佳的抗精神病疗效。目前可用的抗精神病药物仍有许多症状未得到治疗,并且会产生不可接受的副作用。近期对精神分裂症的研究表明,包括谷氨酸、乙酰胆碱和血清素神经递质系统在内的一些潜在新的非D2药物治疗靶点。本综述总结了精神分裂症的主要神经化学理论,并据此研究了新型抗精神病药物可能的治疗靶点。