Potential roles of 5-HT 3 receptor (5-HT 3 R) antagonists in modulating the effects of nicotine

Muhammad Harith Zulkifli, Praveena Viswenaden, Malina Jasamai, Norazrina Azmi, Nor Syafinaz Yaakob

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

5-HT 3 R antagonists such as ondansetron, granisetron and tropisetron have been clinically used to treat nausea and vomiting in chemotherapy patients. However, current study and research revealed novel potentials of these ligands in other diseases like inflammation, Alzheimer's, and drug abuse. Towards utilising these drugs as anti-smoking agents to treat nicotine dependence problem, there are conflicting reports regarding the potential of these ligands in modulating the effects of nicotine in both human and animal behavioural studies. This is complicated by the heterogeneity of 5-HT 3 R itself, cross regulation between nicotinic acetylcholinergic receptor (nAChR) and distinct pharmacological profiles of 5-HT 3 R antagonists. This review gathered existing studies conducted investigating the potential of “-setron” class of 5-HT 3 R antagonists in modulating nicotine effects. We proposed that the mechanism where 5-HT 3 R antagonists mediate the effects of nicotine could be attributed by both direct at 5-HT 3 R and indirect mechanism in nicotine addiction downstream regulation. The indirect mechanism mediated by the 5-HT 3 R antagonist could be through α7 nAChR, 5-HT 1B receptor (5-HT 1B R), 5-HT 1C receptor (5-HT 1C R), calcineurin activity, p38 MAPK level, PPAR-γ and NF-κβ. Our review suggested that future studies should focus on newer 5-HT 3 R antagonist with superior pharmacological profile or the one with multitarget action rather than high selectivity at single receptor.

Original languageEnglish
Article number108630
JournalBiomedicine and Pharmacotherapy
Volume112
DOIs
Publication statusPublished - 1 Apr 2019

Fingerprint

Serotonin Receptors
Nicotine
Serotonin
tropisetron
Nicotinic Receptors
Pharmacology
Granisetron
Receptor, Serotonin, 5-HT1B
Ligands
Ondansetron
Tobacco Use Disorder
Peroxisome Proliferator-Activated Receptors
Calcineurin
p38 Mitogen-Activated Protein Kinases
Nausea
Substance-Related Disorders
Vomiting
Smoking
Inflammation
Drug Therapy

Keywords

  • 5-HT receptor
  • Addiction
  • Nicotine
  • Serotonin
  • Smoking

ASJC Scopus subject areas

  • Pharmacology

Cite this

Potential roles of 5-HT 3 receptor (5-HT 3 R) antagonists in modulating the effects of nicotine . / Zulkifli, Muhammad Harith; Viswenaden, Praveena; Jasamai, Malina; Azmi, Norazrina; Yaakob, Nor Syafinaz.

In: Biomedicine and Pharmacotherapy, Vol. 112, 108630, 01.04.2019.

Research output: Contribution to journalReview article

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