自从1950年代发现氯丙嗪以来,抗精神病药物一直是治疗精神分裂症的基石,都减弱了多巴胺-2受体的多巴胺传递.从那时起,精神分裂症的药物开发导致副作用和耐受性的改善,和有限的疗效改善,除了氯氮平.然而,氯氮平疗效更大的原因尚不清楚,尽管投入了巨大的努力和资源。我们对文献进行了全面回顾,以确定先前测试的命运,非多巴胺-2受体实验治疗。总的来说,我们纳入了1970年至2017年期间的250项研究,包括谷氨酸能治疗,血清素能,胆碱能,神经肽能,基于激素,多巴胺能,新陈代谢,维生素/自然疗法,组胺能,感染/炎症,和各种机制。尽管有几个有希望的目标,如NMDA和α7烟碱受体的变构调节,我们不能自信地说,本综述涵盖的任何一种机制上新颖的实验性治疗方法对精神分裂症的治疗绝对有效,并且可用于临床.我们讨论了在开发精神分裂症的非多巴胺-2受体治疗方面相对缺乏进展的潜在原因,并为未来寻求精神分裂症新药开发的努力提供了建议。
Since the discovery of chlorpromazine in the 1950\'s, antipsychotic drugs have been the cornerstone of treatment of schizophrenia, and all attenuate dopamine transmission at the dopamine-2 receptor. Drug development for schizophrenia since that time has led to improvements in side effects and tolerability, and limited improvements in efficacy, with the exception of clozapine. However, the reasons for clozapine\'s greater efficacy remain unclear, despite the great efforts and resources invested therewith. We performed a comprehensive review of the literature to determine the fate of previously tested, non-dopamine-2 receptor experimental treatments. Overall we included 250 studies in the review from the period 1970 to 2017 including treatments with glutamatergic, serotonergic, cholinergic, neuropeptidergic, hormone-based, dopaminergic, metabolic, vitamin/naturopathic, histaminergic, infection/inflammation-based, and miscellaneous mechanisms. Despite there being several promising targets, such as allosteric modulation of the NMDA and α7 nicotinic receptors, we cannot confidently state that any of the mechanistically novel experimental treatments covered in this review are definitely effective for the treatment of schizophrenia and ready for clinical use. We discuss potential reasons for the relative lack of progress in developing non-dopamine-2 receptor treatments for schizophrenia and provide recommendations for future efforts pursuing novel drug development for schizophrenia.