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 microg per mouse i.c.v. ) prevented antinociception induced by both amitriptyline (15 mg kg(-1) s.c.) and clomipramine (25 mg kg(-1) s.c.). The K(ATP) channel blocker gliquidone (0.1-1.0 microg per mouse i.c.v.) prevented antinociception produced by amitriptyline and clomipramine whereas the K(ATP) channel openers minoxidil (10 microg per mouse i. c.v.) and pinacidil (25 microg per mouse i.c.v.) potentiated tricyclic antidepressant-induced analgesia. The administration of the Ca(2+)-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, K(ATP) and Ca(2+)-gated) which, therefore, represent a step in the transduction mechanism of tricyclic antidepressant analgesia.
Galeotti
N
N
Department of Pharmacology, University of Florence, Viale G. Pieraccini 6, I-50139, Florence, Italy.
Ghelardini
C
C
Bartolini
A
A
D000639:Amitriptyline / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002997:Clomipramine / Q000494:pharmacology*; D007276:Injections, Intraventricular; D051662:Kv1.1 Potassium Channel; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011930:Reaction Time / Q000187:drug effects
D000929:Antidepressive Agents, Tricyclic; C496947:Kcna1 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D000639:Amitriptyline; D002997:Clomipramine; D002118:Calcium