BLOCK OF POTASSIUM CURRENTS IN RAT ISOLATED SYMPATHETIC NEURONS BY TRICYCLIC ANTIDEPRESSANTS AND STRUCTURALLY RELATED-COMPOUNDS

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 muM, imipramine, amitriptyline and chlorpromazine all blocked the delayed rectifier K+ current (I(Kv)) 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 I(Kv) 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 muM) were 2-3 fold more potent at inhibiting the sustained K+ current (mostly I(Kv)) than the transient K+ current (mostly I(A)). Tacrine, however, was equally effective in blocking both components.