Abstract
Neuropeptides and G protein-coupled receptors (GPCRs) have long been,
and continue to be, one of the most popular target classes for drug
discovery in CNS disorders, including alcohol use disorder (AUD). Yet,
orphaned neuropeptide systems and receptors (oGPCR), that have no known
cognate receptor or ligand, remain understudied in drug discovery and
development. Orphan neuropeptides and oGPCRs are abundantly expressed
within the brain and represent an unprecedented opportunity to address
brain function and may hold potential as novel treatments for disease.
Here we describe the current literature regarding orphaned neuropeptides
and oGPCRs implicated in AUD. Specifically, in this review we focus on
the orphaned neuropeptide cocaine and amphetamine regulated transcript
(CART), and several oGPCRs that have been directly implicated in AUD;
GPR6, GPR26, GPR88, GPR139, GPR158, and discuss their potential and
pitfalls as novel treatments and progress in identifying their cognate
receptors or ligands.