Alcohol addiction- metabotropic glutamate receptor subtype 5 and its ligands

How they all come together?

Jaya Kumar, Zalina Ismail, Nurul Hazwani Hatta, Najwa Baharuddin, Hermizi Hapidin, Yvonne Tee Get Bee, Sze Wei Yap, Rashidi Mohamed Pakri Mohamed

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl-6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.

Original languageEnglish
Pages (from-to)907-915
Number of pages9
JournalCurrent Drug Targets
Volume19
Issue number8
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Metabotropic Glutamate 5 Receptor
Metabotropic Glutamate Receptors
Alcoholism
Alcohols
Ligands
Modulators
Pharmacology
Protein Kinase C-epsilon
Neuronal Plasticity
Drug and Narcotic Control
Cell signaling
Alcohol Drinking
Isoenzymes
Transcription
Motivation
Emotions
Pharmaceutical Preparations
Neurons
Brain
Recurrence

Keywords

  • Alcohol addiction
  • Calmodulin
  • Ethanol
  • Homer
  • MGlu5
  • Postsynaptic density proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Alcohol addiction- metabotropic glutamate receptor subtype 5 and its ligands : How they all come together? / Kumar, Jaya; Ismail, Zalina; Hatta, Nurul Hazwani; Baharuddin, Najwa; Hapidin, Hermizi; Bee, Yvonne Tee Get; Yap, Sze Wei; Pakri Mohamed, Rashidi Mohamed.

In: Current Drug Targets, Vol. 19, No. 8, 01.01.2018, p. 907-915.

Research output: Contribution to journalReview article

Kumar, Jaya ; Ismail, Zalina ; Hatta, Nurul Hazwani ; Baharuddin, Najwa ; Hapidin, Hermizi ; Bee, Yvonne Tee Get ; Yap, Sze Wei ; Pakri Mohamed, Rashidi Mohamed. / Alcohol addiction- metabotropic glutamate receptor subtype 5 and its ligands : How they all come together?. In: Current Drug Targets. 2018 ; Vol. 19, No. 8. pp. 907-915.
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