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

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Abstract
1. 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. 2. At a concentration of 10 microM, 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. 3. 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. 4. 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. 5. Amitriptyline, chlorpromazine and imipramine (at 10 microM) 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.