Antinociception induced by amitriptyline and imipramine is mediated by alpha(2A)-adrenoceptors

The involvement of alpha(2)-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigate d in mice by using the hot-plate and abdominal constriction tests. The anti nociception produced by amitriptyline (15 mg/kg, i.p.) and imipramine (15 m g/kg, i.p.) was prevented by reserpine (2 mg/kg, i.p.) and yohimbine (3 - 1 0 mg/kg, i.p.) but not by naloxone (1 mg/kg, i.p.), atropine (5 mg/kg, i.p. ), CGP 35348 (100 mg/kg, i.p.) and prazosin (1 mg/kg, i.p.). On the basis o f the above data, it can be postulated that amitriptyline and imipramine ex erted their antinociceptive effect by activation of alpha(2)-adrenoceptors. Administration of the alpha(2A)-adrenoceptor antagonist BRL 44408 (1 mg/kg , i.p,) prevented amitriptyline and imipramine antinociception, whereas the alpha(2B/C)-adrenoceptor antagonist ARC239 (10 mg/kg, i.p.) was ineffectiv e. These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of alpha(2A)-adre noceptors. Neither tricyclic antidepressants nor the antagonists used impai red mouse performance evaluated by the rota-rod and hole-board tests.