The discovery of receptor-receptor interactions in the early 1980s, together with a more accurate focusing of allosteric mechanisms in proteins, expanded the knowledge on the G protein-coupled receptor (GPCR)-mediated signaling processes. GPCRs were seen to operate not only as monomers, but also as quaternary structures shaped by allosteric interactions. These integrative mechanisms can change the function of the GPCRs involved, leading to a sophisticated dynamic of the receptor assembly in terms of modulation of recognition and signaling. In this context, the heterodimeric complex formed by the adenosine A_2A and the dopamine D₂ receptors likely represents a prototypical example. The pharmacological evidence obtained, together with the tissue distribution of the A_2A-D₂ heteromeric complexes, suggested they could represent a target for new therapeutic strategies addressing significant disorders of the central nervous system. The research findings and the perspectives they offer from the therapeutic standpoint are the focus of the here presented discussion.

在1980年代初期，受体与受体相互作用的发现以及蛋白质中变构机制的更精确聚焦，扩大了对G蛋白偶联受体（GPCR）介导的信号传导过程的认识。观察到GPCR不仅作为单体起作用，而且作为由变构相互作用形成的四级结构起作用。这些整合机制可以改变所涉及的GPCR的功能，从而导致受体组装在识别和信号传递调制方面的复杂动态。在这种情况下，由腺苷A _2A和多巴胺D ₂受体形成的异二聚体复合物可能代表了一个典型的例子。获得的药理证据以及A _2A的组织分布-D ₂异聚复合物，表明它们可以代表针对中枢神经系统重大疾病的新治疗策略的靶标。他们从治疗角度出发的研究发现和观点是本文讨论的重点。