Bruce Blough, Ojas Namjoshi · 2020 · Handbook of experimental pharmacology · Springer · added 2026-04-24
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 Show more
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. Show less