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Small Molecule Neuropeptide S and Melanocortin 4 Receptor Ligands as Potential Treatments for Substance Use Disorders

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Substance Use Disorders

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 258))

Abstract

There is a vital need for novel approaches and biological targets for drug discovery and development. Treatment strategies for substance use disorders (SUDs) to date have been mostly ineffective other than substitution-like therapeutics. Two such targets are the peptide G-protein-coupled receptors neuropeptide S (NPS) and melanocortin 4 (MC4). Preclinical evidence suggests that antagonists, inverse agonists, or negative allosteric modulators of these receptors might be novel therapeutics for SUDs. NPS is a relatively unexplored receptor with high potential for treating SUD. MC4 has a strong link to early-onset obesity, and emerging evidence suggests significant overlap between food-maintained and drug-maintained behaviors making MC4 an intriguing target for SUD. This chapter provides an overview of the literature in relation to the roles of NPS and MC4 in drug-seeking behaviors and then provides a medicinal chemistry-based survey of the small molecule ligands for each receptor.

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Authors and Affiliations

  1. Center for Drug Discovery, RTI International, Research Triangle Park, NC, USA

    Bruce Blough & Ojas Namjoshi

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  1. Bruce Blough
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  2. Ojas Namjoshi
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Correspondence to Bruce Blough .

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  1. Wake Forest School of Medicine, Winston-Salem, NC, USA

    Michael A. Nader

  2. Addiction Institute of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Yasmin L. Hurd

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Blough, B., Namjoshi, O. (2019). Small Molecule Neuropeptide S and Melanocortin 4 Receptor Ligands as Potential Treatments for Substance Use Disorders. In: Nader, M., Hurd, Y. (eds) Substance Use Disorders. Handbook of Experimental Pharmacology, vol 258. Springer, Cham. https://doi.org/10.1007/164_2019_313

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