Block of potassium currents in rat isolated sympathetic neurones by tricyclic antidepressants and structurally related compounds

Abstract

The block of K+ currents by the tricyclic antidepressants (TCAs), imipramine and amitriptyline and three structurally related compounds, chlorpromazine, tacrine and carbamazepine was investigated in rat isolated sympathetic neurones by whole‐cell voltage‐clamp recording. At a concentration of 10 μm, imipramine, amitriptyline and chlorpromazine all blocked the delayed rectifier K+ current (IKv) by about the same extent, 54%, 47% and 53%. Tacrine was less effective (10%) while carbamazepine was ineffective at all concentrations tested. The degree of block by the four effective compounds was relatively independent of the size of the voltage‐step. Neither the activation nor the inactivation rates of IKv were altered by the blocking drugs. Concentration‐response relationships for imipramine and tacrine showed that imipramine was about 7 fold more potent than tacrine but that the maximum inhibition and the Hill slope were the same for both compounds. Amitriptyline, chlorpromazine and imipramine (at 10 μm) were 2–3 fold more potent at inhibiting the sustained K+ current (mostly IKv) than the transient K+ current (mostly IA). Tacrine, however, was equally effective in blocking both components. 1993 British Pharmacological Society