Effect of Tizanidine, Rilmenidine, and Yohimbine on Naloxon-Induced Morphine Withdrawal Syndrome in Mice

Valiollah Hajhashemi; Mohsen Minaiyan; Mohammad Seyedabadi

doi:10.22037/ijpr.2010.708

IJ Pharmaceutical Research

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https://doi.org/10.22037/ijpr.2010.708

Effect of Tizanidine, Rilmenidine, and Yohimbine on Naloxon-Induced Morphine Withdrawal Syndrome in Mice

Author(s):

Valiollah Hajhashemi^1,*,

Mohsen Minaiyan¹,

Mohammad Seyedabadi¹

1Department of Pharmacology and the Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

IJ Pharmaceutical Research:Vol. 6, issue 2; 115-121

Published online:Nov 20, 2010

Article type:Research Article

Received:Feb 21, 2006

Accepted:Jun 21, 2006

How to Cite:Valiollah HajhashemiMohsen MinaiyanMohammad SeyedabadiEffect of Tizanidine, Rilmenidine, and Yohimbine on Naloxon-Induced Morphine Withdrawal Syndrome in Mice.Iran J Pharm Res.6(2):e128319.https://doi.org/10.22037/ijpr.2010.708.

Abstract

In this study using clonidine (a mixed α₂ /I₁ receptors agonist), tizanidine (pure α₂-receptor agonist), rilmenidine (I₁ receptor agonist) and yohimbine (α₂-receptor antagonist), we tried to clarify the role of imidazoline and α₂-receptors in morphine withdrawal syndrome.

Morphine-dependence was induced by administration of increasing doses of morphine in mice. After the last administration of morphine, clonidine (0.3 mg/kg, i.p.), tizanidine (1 and 2 mg/kg, i.p.) and rilmenidine (1.5 and 3 mg/kg, i.p.), with / without pretreatment with yohimbine (1 mg/kg, i.p.) were administered 30 min before naloxone (5 mg/kg, i.p.) challenge. Withdrawal symptoms including: jumping, ptosis, piloerection, tremor and diarrhea were recorded.

Rilmenidine (3 mg/kg) decreased naloxone-induced jumping and this effect was partially inhibited by yohimbine. Rilmenidine (1.5 mg/kg), tizanidine and clonidine had no significant effect on jumping. None of drugs influenced ptosis. All drugs increased piloerection and decreased diarrhea. Clonidine and tizanidine decreased tremor.

We conclude that Imidazoline receptors as well as α₂ receptors are involved in morphine withdrawal symptoms and yohimbine as an α₂-antagonist can suppress at least some effects of imidazoline agonists. It is suggested that α₂-receptors are located down-stream to imidazoline receptors and their blockade can inhibit imidazoline effects.

Keywords

Clonidine Imidazoline receptors

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Author(s):

Valiollah Hajhashemi:[PubMed][Scholar]
Mohsen Minaiyan:[PubMed][Scholar]
Mohammad Seyedabadi:[PubMed][Scholar]