Clozapine is the gold-standard agent for treatment resistant schizophrenia but its mechanism of action remains unclear. There is emerging evidence of the potential role of the GABA_B receptor in the pathogenesis of schizophrenia. It has been hypothesised that clozapine can mediate its actions via the GABA_B receptor. Baclofen is currently recognised as the prototype GABA_B receptor agonist. There are some potential clinical similarities between clozapine and baclofen. Indeed, baclofen has been previously proposed for use as an antipsychotic agent. Our analysis of the X-ray crystal structure of GABA_B receptor along with molecular docking calculations, suggests that clozapine could directly bind to the GABA_B receptor similar to that of baclofen. This finding could lead to a better understanding of the pharmacological uniqueness of clozapine, potential development of a biomarker for treatment resistant schizophrenia and the development of more targeted treatments leading to personalisation of treatment.

氯氮平是治疗耐药性精神分裂症的金标准药物，但其作用机制仍不清楚。越来越多的证据表明 GABA _B受体在精神分裂症发病机制中的潜在作用。据推测，氯氮平可以通过 GABA _B受体介导其作用。巴氯芬目前被认为是原型 GABA _B受体激动剂。氯氮平和巴氯芬之间存在一些潜在的临床相似性。事实上，巴氯芬以前曾被提议用作抗精神病药。_{我们对 GABA B}受体的 X 射线晶体结构的分析以及分子对接计算表明，氯氮平可以直接与 GABA _B结合受体与巴氯芬相似。这一发现可能有助于更好地了解氯氮平的药理学独特性、潜在的治疗耐药性精神分裂症生物标志物的开发以及更有针对性的治疗方法的开发，从而实现治疗的个性化。