Fluoxetine inhibits L-type Ca2+ and transient outward K+ currents in rat ventricular myocytes.

摘要: The most common cardiovascular side effects of antidepressants are cardiac arrhythmias and orthostatic hypotension. Little is known, however, about the mechanisms by which these adverse reactions may occur, especially with regard to newer drugs such as fluoxetine. We hypothesized that have an electrophysiological basis at level myocyte. Thus, we investigated fluoxetine other on action potentials ionic currents rat ventricular myocytes using amphotericin B perforated patch clamp technique. Fluoxetine (10 microM) prolonged potential duration (APD50) 146.7 +/- 12.9% control value without altering resting membrane potential. sertraline potently inhibited L-type Ca2+ current (IC50 = 2.82 2.31 microM, respectively), but did not significantly modify steady-state inactivation. Amitriptyline imipramine had similar, slightly weaker, 3.75 4.05 respectively). attenuated peak transient outward K+ also altered kinetics, shown accelerated decay. change voltage-dependence Sertraline, amitriptyline potencies very similar In contrast tested, trazodone weakly moclobemide no detectable effect. Our comparative pharmacology data suggest selective serotonin reuptake inhibitors, fluoxetine, potent tricyclic in inhibiting currents. These inhibitory contribute complications