Tetrahydroprotoberberines (THPBs) are a class of compounds that target both dopamine D1 and D2 families of receptors, making them attractive candidates for treating substance use disorder (SUD). The binding of some THPBs to serotonin and adrenergic receptors, in addition to dopamine receptors, gives rise to complex pharmacological profiles. Significant progress has been made over the last decade in examining these compounds for their therapeutic potential. Here, we evaluate recent discoveries relating to the neural mechanism and therapeutic effects of THPBs, focusing on compounds that have shown promise in animal models of SUD and preliminary clinical studies. Advancements in structure-activity relationship studies and in silico modeling of THPB binding to dopamine receptors have facilitated the synthesis of novel THPBs with enhanced therapeutic properties and provide insights regarding use of the THPB scaffold to serve as a template for innovative drug designs.

中文翻译：

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四氢原小檗碱：物质使用障碍药物治疗的新来源？

四氢原小檗碱 (THPB) 是一类针对多巴胺 D1 和 D2 受体家族的化合物，使其成为治疗物质使用障碍 (SUD) 的有吸引力的候选药物。除了多巴胺受体外，一些 THPB 与血清素和肾上腺素能受体的结合会产生复杂的药理学特征。在过去十年中，在检查这些化合物的治疗潜力方面取得了重大进展。在这里，我们评估了与 THPB 的神经机制和治疗效果相关的最新发现，重点关注在 SUD 动物模型和初步临床研究中显示出前景的化合物。