Involvement of potassium channels in amitriptyline and clomipramine analgesia.

The effect of the administration of modulators of different subtypes of K+ channels on antinociception induced by the tricyclic antidepressants amitriptyline and clomipramine was evaluated in the mouse hot plate test. The administration of the voltage-gated K+ channel blocker tetraethylammonium (0.01–0.5 mg per mouse i.c.v.) prevented antinociception induced by both amitriptyline (15 mg kg21 s.c.) and clomipramine (25 mg kg21 s.c.). The KATP channel blocker gliquidone (0.1–1.0 mg per mouse i.c.v.) prevented antinociception produced by amitriptyline and clomipramine whereas the KATP channel openers minoxidil (10 mg per mouse i.c.v.) and pinacidil (25 mg per mouse i.c.v.) potentiated tricyclic antidepressant-induced analgesia. The administration of the Ca2+-gated K+ channel blocker apamin (0.1–1.0 ng per mouse i.c.v.) completely prevented amitriptyline and clomipramine analgesia. At the highest effective doses, none of the drugs used induced behavioural side effects or impaired motor coordination, as revealed by the rota-rod test, spontaneous motility or inspection activity, as revealed by the hole board test. The present results demonstrate that central antinociception induced by amitriptyline and clomipramine involves the opening of different subtypes of K+ channels (voltage-gated, KATP and Ca2+-gated) which, therefore, represent a step in the transduction mechanism of tricyclic antidepressant analgesia.