Title:Opioid Withdrawal Syndrome: Emerging Concepts and Novel Therapeutic Targets
VOLUME: 12 ISSUE: 1
Author(s):Ashish K. Rehni, Amteshwar S. Jaggi and Nirmal Singh
Affiliation:Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147002, Punjab, India.
Keywords:Opioid dependence, opioid withdrawal syndrome, adenylyl cyclase superactivation, pharmacological interventions
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 superactivation
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-proteingated
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.
