Orphan G protein-coupled receptors: The role in CNS disorders

Biomed Pharmacother. 2018 Feb;98:222-232. doi: 10.1016/j.biopha.2017.12.056. Epub 2017 Dec 27.


There are various types of receptors in the central nervous system (CNS). G protein-coupled receptors (GPCRs) have the highest expression with a wide range of physiological functions. A newer sub group of these receptors namely orphan GPCRs have been discovered. GPR3, GPR6, GPR17, GPR26, GPR37, GPR39, GPR40, GPR50, GPR52, GPR54, GPR55, GPR85, GPR88, GPR103, and GPR139 are the selected orphan GPCRs for this article. Their roles in the central nervous system have not been understood well so far. However, recent studies show that they may have very important functions in the CNS. Hence, in the present study, we reviewed most recent findings regarding the physiological roles of the selected orphan GPCRs in the CNS. After a brief presentation of each receptor, considering the results from genetic and pharmacological manipulation of the receptors, their roles in the pathophysiology of different diseases and disorders including anxiety, depression, schizophrenia, epilepsy, Alzheimer's disease, Parkinson's disease, and substance abuse will be discussed. At present, our knowledge regarding the role of GPCRs in the brain is very limited. However, previous limited studies show that orphan GPCRs have an important place in psychopharmacology and these receptors are potential new targets for the treatment of major CNS diseases.

Keywords: Anxiety; Brain; Depression; Fatty acids; Neurodegenerative diseases; Orphan GPCR; Seizure.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System Agents / pharmacology
  • Central Nervous System Agents / therapeutic use
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / metabolism*
  • Humans
  • Mental Disorders / drug therapy*
  • Mental Disorders / metabolism*
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Central Nervous System Agents
  • GPR3 protein, human
  • GPR6 protein, human
  • Receptors, G-Protein-Coupled