Block of potassium currents in rat isolated sympathetic neurones 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 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.
Wooltorton
J R
JR
Department of Pharmacology, Royal Free Hospital School of Medicine, London.
Mathie
A
A
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D000929:Antidepressive Agents, Tricyclic; D015221:Potassium Channels; D000639:Amitriptyline