Send to

Choose Destination
ACS Chem Neurosci. 2019 Jan 16;10(1):190-200. doi: 10.1021/acschemneuro.8b00572. Epub 2018 Dec 20.

Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target.

Author information

Department of Medicinal Chemistry, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences , Soochow University , Suzhou , Jiangsu 215123 , China.
Department of Pharmacology and Toxicology, Center for Addiction Research , University of Texas Medical Branch , Galveston , Texas 77555 , United States.


Although G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions, including cognition, mood, movement control, and reward-based learning, and is thus emerging as a novel drug target for central nervous system disorders including schizophrenia, Parkinson's disease, anxiety, and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials, and GPR88 endogenous ligands remain unknown. Despite the recent discovery and early stage study of several GPR88 agonists, such as 2-PCCA, RTI-13951-33, and phenylglycinol derivatives, further research into GPR88 pharmacology, medicinal chemistry, and chemical biology is urgently needed to yield structurally diversified GPR88-specific ligands. Drug-like pharmacological tool function and relevant signaling elucidation will also accelerate the evaluation of this receptor as a viable neurotherapeutic target.


CNS disorders; GPR88; Orphan G protein-coupled receptors (oGPCRs); agonists; drug discovery; neurotherapeutics; striatum

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center