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 (15Êmg/kg,Êi.p.) and imipramine (15Êmg/kg,Êi.p.) was prevented by reserpine (2Êmg/kg,Êi.p.) and yohimbine (3-10Êmg/kg,Êi.p.) but not by naloxone (1Êmg/kg,Êi.p.), atropine (5Êmg/kg,Êi.p.), CGPÊ35348 (100Êmg/kg,Êi.p.) and prazosin (1Êmg/kg,Êi.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 BRLÊ44408 (1Êmg/kg,Êi.p.) prevented amitriptyline and imipramine antinociception, whereas the a2B/C-adrenoceptor antagonist ARCÊ239 (10Êmg/kg,Êi.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