Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
CNS Neurosci Ther. 2011 Feb;17(1):52-7. doi: 10.1111/j.1755-5949.2010.00228.x. Epub 2010 Dec 28.
Over the past two decades the dopamine D2 receptor has been undoubtedly the most widely studied dopamine receptor for the therapeutic treatment of schizophrenia, as the majority of antipsychotics exhibit antagonism at this receptor. However, the cognitive symptoms of the disorder are mostly resistant to the majority of available antipsychotic treatments and, as a result, there is a critical need to develop novel therapies that ameliorate all symptoms. The recognition that dopamine receptors, such as all G protein-coupled receptors (GPCRs), exist as oligomeric complexes has provided new avenues for drug design in the search for novel therapies. Furthermore, that it is now known that dopamine receptors can form heteromers, such as the dopamine D1-D2 receptor heteromer, with pharmacology and function distinct from its constituent receptors, has significantly expanded the range of potential drug targets. The aim of this review is to discuss the therapeutic relevance of these dopamine receptor oligomers to schizophrenia and to address the potential value of dopamine receptor heteromers in the search for new therapeutic strategies.
在过去的二十年中,多巴胺 D2 受体无疑是研究最多的用于治疗精神分裂症的多巴胺受体,因为大多数抗精神病药物在该受体上表现出拮抗作用。然而,该疾病的认知症状大多对抗精神病药物的大多数现有治疗方法具有抗性,因此,迫切需要开发能够改善所有症状的新疗法。人们认识到,多巴胺受体(如所有 G 蛋白偶联受体 (GPCR))作为寡聚复合物存在,为寻找新疗法的药物设计提供了新途径。此外,现在已知多巴胺受体可以形成异源二聚体,例如多巴胺 D1-D2 受体异源二聚体,其药理学和功能与其组成受体不同,这大大扩展了潜在药物靶点的范围。本文的目的是讨论这些多巴胺受体寡聚体与精神分裂症的治疗相关性,并探讨多巴胺受体异源二聚体在寻找新的治疗策略中的潜在价值。