Molecular insights into GPCR mechanisms for drugs of abuse. J Biol Chem 2023 Sep;299(9):105176
Date
08/21/2023Pubmed ID
37599003Pubmed Central ID
PMC10514560DOI
10.1016/j.jbc.2023.105176Scopus ID
2-s2.0-85171147748 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Substance abuse is on the rise, and while many people may use illicit drugs mainly due to their rewarding effects, their societal impact can range from severe, as is the case for opioids, to promising, as is the case for psychedelics. Common with all these drugs' mechanisms of action are G protein-coupled receptors (GPCRs), which lie at the center of how these drugs mediate inebriation, lethality, and therapeutic effects. Opioids like fentanyl, cannabinoids like tetrahydrocannabinol, and psychedelics like lysergic acid diethylamide all directly bind to GPCRs to initiate signaling which elicits their physiological actions. We herein review recent structural studies and provide insights into the molecular mechanisms of opioids, cannabinoids, and psychedelics at their respective GPCR subtypes. We further discuss how such mechanistic insights facilitate drug discovery, either toward the development of novel therapies to combat drug abuse or toward harnessing therapeutic potential.
Author List
Sanchez-Reyes OB, Zilberg G, McCorvy JD, Wacker DAuthor
John McCorvy PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analgesics, OpioidCannabinoids
Hallucinogens
Humans
Models, Molecular
Receptors, G-Protein-Coupled
Receptors, Serotonin
Signal Transduction
