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首页> 外文期刊>Expert opinion on therapeutic targets >The search for novel antipsychotics: pharmacological and molecular targets.
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The search for novel antipsychotics: pharmacological and molecular targets.

机译：寻找新型抗精神病药：药理和分子靶点。

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There can be little doubt that the newer, atypical, antipsychotic drugs provide improved treatment for many patients suffering from schizophrenia. However, the significant gains in tolerability produced by these drugs have not generally been accompanied by major advances in clinical efficacy. In particular, negative and cognitive symptoms, which may represent the core deficit of the disease, remain inadequately treated. There is, therefore, a pressing need for more effective drugs. A number of drug discovery and development programmes are currently underway in parallel with significant research into the basic neurobiology of the disease. All antipsychotic drugs currently used in the clinic are antagonists at dopamine D2 receptors, and dopamine neurotransmission seems likely to remain a major biological target for research. However, novel approaches to modulate dopaminergic neurotransmission selectively in relevant brain regions may be required. In addition, a range of non-dopaminergic targets including glutamate, serotonin, neurokinins and acetylcholine are also of major interest. It is likely, however, that the importance of many of these targets may lie in their relationships to and interactions with dopaminergic mechanisms. Finally, advances in genetics and molecular biology are identifying genes associated with a susceptibility to develop schizophrenia. It remains to be seen whether or not these genes and their associated proteins will provide molecular targets for successful drug discovery.
机译：毫无疑问，新型的非典型抗精神病药可以为许多精神分裂症患者提供更好的治疗。然而，这些药物所产生的耐受性的显着提高通常并未伴随着临床疗效的重大进步。尤其是，可能代表疾病核心缺陷的阴性和认知症状仍未得到充分治疗。因此，迫切需要更有效的药物。目前正在进行许多药物发现和开发计划，同时对该疾病的基本神经生物学进行了重大研究。目前临床上使用的所有抗精神病药物都是多巴胺D2受体的拮抗剂，多巴胺的神经传递似乎仍将是研究的主要生物学目标。然而，可能需要新颖的方法来选择性地调节相关脑区域中的多巴胺能神经传递。此外，包括谷氨酸盐，5-羟色胺，神经激肽和乙酰胆碱在内的一系列非多巴胺能靶标也引起了人们的极大兴趣。但是，许多这些靶标的重要性很可能在于它们与多巴胺能机制的关系和相互作用。最后，遗传学和分子生物学的进展正在鉴定与易患精神分裂症相关的基因。这些基因及其相关蛋白是否会为成功的药物发现提供分子靶点，还有待观察。

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