Compounds that target D2-like dopamine receptors (DRs) are currently used as therapeutics for several neuropsychiatric disorders including schizophrenia (antagonists) and Parkinson's disease (agonists). However, as the D₂R and D₃R subtypes are highly homologous, creating compounds with sufficient subtype-selectivity as well as drug-like properties for therapeutic use has proved challenging. This review summarizes the progress that has been made in developing D₂R- or D₃R-selective antagonists and agonists, and also describes the experimental conditions that need to be considered when determining the selectivity of a given compound, as apparent selectivity can vary widely depending on assay conditions. Future advances in this field may take advantage of currently available structural data to target alternative secondary binding sites through creating bivalent or bitopic chemical structures. Alternatively, the use of high-throughput screening techniques to identify novel scaffolds that might bind to the D₂R or D₃R in areas other than the highly conserved orthosteric site, such as allosteric sites, followed by iterative medicinal chemistry will likely lead to exceptionally selective compounds in the future. More selective compounds will provide a better understanding of the normal and pathological functioning of each receptor subtype, as well as offer the potential for improved therapeutics.

目前，靶向D2样多巴胺受体（DRs）的化合物可用于治疗多种神经精神疾病，包括精神分裂症（拮抗剂）和帕金森氏病（激动剂）。然而，由于D ₂ R和D ₃ R亚型是高度同源的，因此创建具有足够亚型选择性以及药物样性质用于治疗用途的化合物已被证明具有挑战性。这篇综述总结了在开发D ₂ R-或D ₃方面所取得的进展R-选择性拮抗剂和激动剂，还描述了确定给定化合物的选择性时需要考虑的实验条件，因为表观选择性可能会因测定条件而异。该领域的未来进展可能会利用当前可用的结构数据，通过创建二价或双位化学结构来靶向备选的二级结合位点。或者，使用高通量筛选技术来鉴定可能与D ₂ R或D ₃结合的新型支架R在高度保守的正构位点以外的区域（例如变构位点）中，随后进行迭代药物化学反应，很可能会在将来导致异常选择性的化合物。更具选择性的化合物将提供对每种受体亚型的正常和病理功能的更好理解，并提供改进治疗方法的潜力。