Electrophysiologic effects of pirmenol, its metabolite 2, and enantiomers, on cardiac Purkinje fibers.
We used standard microelectrode techniques to study the electrophysiologic effects of pirmenol, its cis-(+) and cis-(-) enantiomers, and its metabolite 2 on canine Purkinje fibers. The parent compound and both enantiomers significantly reduced the amplitude and Vmax of phase 0 of the action potential (AP) and shortened AP duration (APD). No significant differences were detected in the concentration-dependent effects on AP characteristics among these three compounds. Metabolite 2 caused similar changes in the amplitude and Vmax of phase 0, but they were of lesser magnitude. In contrast to the parent compound, metabolite 2 markedly prolonged repolarization. The use-dependent effects of pirmenol and metabolite 2 were studied. At 10(-5) M, the time constant of onset of use-dependent block (tau on) for pirmenol was 10.4 +/- 0.4 (mean +/- SEM) beats; for metabolite 2, it was 7.4 +/- 0.8 beats (p < 0.05). The time constants of recovery from use-dependent block (tau off) were comparable: pirmenol 18 +/- 2 s and metabolite 2 21 +/- 6 s (p > 0.05). Pirmenol and its enantiomers have comparable local anesthetic effects. In contrast to pirmenol, its metabolite 2 prolongs AP duration.
Lee
J H
JH
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D066298:In Vitro Techniques; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C024318:pirmenol