Jpn. J. Pharmacol. 82 (2), 130-137 (2000)


Antinociception Induced by Amitriptyline and Imipramine
Is Mediated by a2A-Adrenoceptors

Carla Ghelardini, Nicoletta Galeotti and Alessandro Bartolini


Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G. Pieraccini, 6, I-50139 Florence, Italy

Abstract: The involvement of a2-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigated in mice by using the hot-plate and abdominal constriction tests. The antinociception produced by amitriptyline (15mg/kg,i.p.) and imipramine (15mg/kg,i.p.) was prevented by reserpine (2mg/kg,i.p.) and yohimbine (3-10mg/kg,i.p.) but not by naloxone (1mg/kg,i.p.), atropine (5mg/kg,i.p.), CGP35348 (100mg/kg,i.p.) and prazosin (1mg/kg,i.p.). On the basis of the above data, it can be postulated that amitriptyline and imipramine exerted their antinociceptive effect by activation of a2-adrenoceptors. Administration of the a2A-adrenoceptor antagonist BRL44408 (1mg/kg,i.p.) prevented amitriptyline and imipramine antinociception, whereas the a2B/C-adrenoceptor antagonist ARC239 (10mg/kg,i.p.) was ineffective. These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of a2A-adrenoceptors. Neither tricyclic antidepressants nor the antagonists used impaired mouse performance evaluated by the rota-rod and hole-board tests.

Keywords: Analgesia, Amitriptyline, Imipramine, a2A-Adrenoceptor, Tricyclic antidepressant


Copyright The Japanese Pharmacological Society 2000

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