Opioid withdrawal syndrome: Emerging concepts and novel therapeutic targets

Ashish K. Rehni, Amteshwar S. Jaggi, Nirmal Singh

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

Opioid withdrawal syndrome is a debilitating manifestation of opioid dependence and responds poorly to the available clinical therapies. Studies from various in vivo and in vitro animal models of opioid withdrawal syndrome have led to understanding of its pathobiology which includes complex interrelated pathways leading to adenylyl cyclase super-activation based central excitation. Advancements in the elucidation of opioid withdrawal syndrome mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the neurobiology of opioid withdrawal syndrome and its therapeutic target recptors like calcitonin gene related peptide receptors (CGRP), N-methyl-D-aspartate (NMDA) receptors, gamma aminobutyric acid receptors (GABA), G-protein-gated inwardly rectifying potassium (GIRK) channels and calcium channels. The present review further details the potential role of second messengers like calcium (Ca2+)/calmodulin-dependent protein kinase (CaMKII), nitric oxide synthase, cytokines, arachidonic acid metabolites, corticotropin releasing factor, fos and src kinases in causing opioid withdrawal syndrome. The exploitation of these targets may provide effective therapeutic agents for the management of opioid dependence-induced abstinence syndrome.

Original languageEnglish (US)
Pages (from-to)112-125
Number of pages14
JournalCNS and Neurological Disorders - Drug Targets
Volume12
Issue number1
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Adenylyl cyclase superactivation
  • Opioid dependence
  • Opioid withdrawal syndrome
  • Pharmacological interventions

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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