Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
CNS Drugs. 2022 Aug;36(8):787-801. doi: 10.1007/s40263-022-00934-0. Epub 2022 Jul 13.
The neurobiological and neurochemical mechanisms underlying the pathophysiology of bipolar disorder are complex and not yet fully understood. From circadian disruption to neuroinflammation, many pathways and signaling molecules are important contributors to bipolar disorder development, some specific to a disease subtype or a cycling episode. Pharmacological agents for bipolar disorder have shown only partial efficacy, including mood stabilizers and antipsychotics. The purinergic hypothesis for bipolar disorder emerges in this scenario as a promising target for further research and drug development, given its role in neurotransmission and neuroinflammation that results in behavioral and mood regulation. Here, we review the basic concepts of purinergic signaling in the central nervous system and its contribution to bipolar disorder pathophysiology. Allopurinol and novel P2X7 receptor antagonists are promising candidates for treating bipolar disorder. We further explore currently available pharmacotherapies and the emerging new purinergic targets for drug development in bipolar disorder.
双相障碍病理生理学的神经生物学和神经化学机制复杂，尚未完全阐明。从昼夜节律紊乱到神经炎症，许多途径和信号分子是双相障碍发展的重要贡献者，其中一些特定于疾病亚型或循环发作。双相障碍的药物治疗仅显示部分疗效，包括心境稳定剂和抗精神病药。在这种情况下，嘌呤能假说作为进一步研究和药物开发的有前途的靶点出现，因为它在神经传递和神经炎症中起作用，从而调节行为和情绪。在这里，我们回顾了中枢神经系统中嘌呤能信号的基本概念及其对双相障碍病理生理学的贡献。别嘌醇和新型 P2X7 受体拮抗剂是治疗双相障碍的有前途的候选药物。我们进一步探讨了目前可用的药物治疗方法和新兴的双相障碍药物开发中的新嘌呤能靶点。
