摘要：

This chapter describes the approaches that have been undertaken in deorphanizing G protein coupled receptor (GPCRs). The chapter also discusses the strategy used to identify the natural ligands for orphan GPCRs. It then describes the status of current knowledge of one deorphanized GPCR, the melaninヽoncentrating hormone (MCH) receptor, as an example of the impact of GPCR deorphanization on drug discovery. It also reviews two other deorphanized GPCRs, the prolactin releasing peptides (PrRP) system, and the neuropeptide B and W (NPB and NPW) system, and evaluates their therapeutic implications. Numerous drug discovery programs have been initiated as soon as the natural ligands of orphan GPCR have been found. The OFQ/nociceptin system is sought for its involvement for pain and anxiety, and the orexin/hypocretin system for narcolepsy and food intake. The ghrelin, NPW, and melaninヽoncentrating hormone (MCH) systems are the targets of drug discovery programs aimed at obesity, while the metastin (KiSS/kisspeptin) system seems to have potential in the regulation of metastasis.

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