Effects of pirmenol HCl on electrophysiologic properties of cardiac Purkinje fibers.

We studied the effects of pirmenol hydrochloride (CI 845), cis-(+/-)-alpha-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenyl-2-pyridinemethanol monohydrochloride, on the electrophysiologic properties of canine cardiac Purkinje fibers having normal (fast response) action potentials. CI 845 greater than or equal to 1 X 10(-6) M depressed both maximum upstroke velocity of phase 0 and automaticity. CI 845 greater than or equal to 1 X 10(-5) M significantly decreased action potential amplitude and duration measured at 50% repolarization and prolonged action potential duration measured at full repolarization. In addition, this concentration depressed membrane responsiveness and prolonged the effective refractory period and conduction time. All changes were reversible following superfusion with drug-free Tyrode solution. Increasing extracellular potassium ([K+]0) from 4 mM to 6 mM did not potentiate the CI 845-induced changes. CI 845 1 X 10(-5) M decreased automaticity of slow response action potentials studied in a Na+-free solution but had no effect on the action potential characteristics of these spontaneously discharging fibers. In blood superfusion studies, plasma levels of 0.1--3.0 micrograms/ml CI 845 affected the action potential characteristics in a manner similar to concentrations ranging from 1 X 10(-6) to 1 X 10(-5) M CI 845 in Tyrode solution. At plasma levels greater than or equal to 1.1 micrograms/ml, CI 845 induced a significant prolongation of the electrocardiographic PR interval. These studies indicate that CI 845 has effects on the action potential and ECG similar but not identical to those of 'local anesthetic' antiarrhythmic agents.