G protein-coupled receptors as targets for transformative neuropsychiatric therapeutics

G protein-coupled receptors (GPCRs) constitute the largest family of druggable genes in the human genome. Even though perhaps 30% of approved medications target GPCRs, they interact with only a small number of them. Here, we consider whether there might be new opportunities for transformative therapeutics for neuropsychiatric disorders by specifically targeting both known and understudied GPCRs. Using psychedelic drugs that target serotonin receptors as an example, we show how recent insights into the structure, function, signaling, and cell biology of these receptors have led to potentially novel therapeutics. We next focus on the possibility that nonpsychedelic 5-HT2A receptor agonists might prove to be safe and rapidly acting antidepressants. Finally, we examine understudied and orphan GPCRs using the MRGPR family of receptors as an example.

Automated summary

This article discusses the possibility of new transformative therapeutics for neuropsychiatric disorders by specifically targeting known and understudied GPCRs. Taking psychedelic drugs that target serotonin receptors as an example, recent insights into the structure, function, signaling, and cell biology of these receptors have led to potentially novel therapeutics. It also explores the potential of nonpsychedelic 5-HT2A receptor agonists as safe and rapidly acting antidepressants, and examines understudied and orphan GPCRs using the MRGPR family of receptors as an example.