Effects of tetracyclic antidepressant drugs on the electrophysiological properties of canine cardiac Purkinje fibres.
The direct actions of the tetracyclic antidepressant drugs maprotiline and mianserin on isolated, superfused, canine cardiac Purkinje fibres were examined in vitro using glass microelectrode recordings and programmed stimulation. Purkinje fibre bundles were driven at 1.25 Hz and electrophysiological measurements were made before and 40 mins after addition of maprotiline or mianserin to the perfusate in a concentration of 50, 250 or 1000 ng/mL. In nondepressed Purkinje fibres maprotiline but not mianserin caused slight resting hyperpolarization at 50 ng/mL while neither drug affected resting membrane potential at the higher concentrations. Maprotiline but not mianserin caused dose-related reductions of action potential amplitude, maximal upstroke velocity of phase 0 (Vmax) and conduction velocity; and both drugs reduced action potential duration and effective refractory period. In depressed fibres mianserin alone was tested at concentrations of 250 and 1000 ng/mL, and was again found to have no effect on resting membrane potential, amplitude, Vmax or effective refractory period although it did reduce action potential duration by 17% and conduction velocity by 19%. Thus, the direct cellular electrophysiological actions of maprotiline resembled those reported for the tricyclic anti-depressants. The weak or absent depressant effects of mianserin on amplitude, Vmax and conduction velocity distinguish this drug from maprotiline and the tricyclic anti-depressants and may explain the low incidence of toxic ventricular arrhythmias and conduction disturbances associated with the clinical use of mianserin.
Brennan
F J
FJ
Department of Medicine, Queen's University, Kingston, Ontario.
Cassidy
D M
DM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D003864:Depression, Chemical; D004285:Dogs; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D008376:Maprotiline / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008803:Mianserin / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D000873:Anthracenes; D008803:Mianserin; D008376:Maprotiline