Mamta Gautam, Anoop Tewari, Soni Singh, Chetna Dixit, K. Gopalan Raghu,
Prem Prakash and Onkar Tripathi*
Physiology Division, Central Drug Research Institute, Chhattar Manzil Palace, Post Box 173, Lucknow-226 001, India
*ÊTo whom correspondence should be addressed.
Abstract: The action of fendiline on cardiac electrical activity was investigated in guinea pig papillary muscle by monitoring frequency- and time-dependent changes in membrane potential, action potential (AP) configuration and conduction velocity. Isolated guinea pig papillary muscles driven at 0.1 to 3ÊHz showed a concentration-dependent reduction of +Vmax, overshoot, and AP duration at -20ÊmV (APD20) in the presence of fendiline (1-320ÊmM), reflecting inhibition of Na+ and L-type Ca2+ channels, respectively. No significant change in resting potential and AP duration at 90% repolarization (APD90) were observed. Inhibition of +Vmax and APD20 was more prominent at higher frequency of stimulation (2ÊHz) than at lower ones (0.2ÊHz), demonstrating frequency-dependent block of Na+ and Ca2+ channels including an open channel block. A good relationship between changes in +Vmax and APD20 suggested some commonality in the mechanism of inhibition of Na+ and Ca2+ channels by fendiline. Time-dependence of effects of fendiline, observed in
Keywords: Fendiline, Diphenylalkylamine, Na+ channel, Ca2+ channel blocker, Cardiac action potential
Copyright© The Japanese Pharmacological Society 2000
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