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Electrophysiological effects of E‐3753, a new antiarrhythmic drug, in guinea‐pig ventricular muscle
Author(s) -
Delpón Eva,
Valenzuela Carmen,
Tamargo Juan
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11909.x
Subject(s) - electrophysiology , membrane potential , refractory period , resting potential , medicine , isoprenaline , chemistry , guinea pig , endocrinology , biophysics , stimulation , biology
1 The electrophysiological effects of E‐3753, a new antiarrhythmic drug, were studied in guinea‐pig papillary muscles. 2 E‐3753 (10 −7 ‐10 −4 m ) produced a concentration‐dependent decrease in the action potential amplitude and V max of the upstroke, shortened the action potential duration (APD) and shifted the resting membrane potential to less negative values. E‐3753 also shortened the effective refractory period (ERP), lengthening the ERP relative to APD. 3 E‐3753 (10 −5 m ) shifted the membrane responsiveness curve along the voltage axis to more negative potentials. 4 In the presence of E‐3753 (10 −5 m ) trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in V max (onset rate at 3 Hz, 0.05 ± 0.009 per action potential), to a new steady‐state level. This use‐dependent V max block was augmented at higher rates of stimulation. The time constant for the recovery of V max from the use‐dependent block was 41.1 ± 4.8 s. 5 E‐3753 (10 −5 ‐10 −4 m ) had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 m m KCl. 6 The slow onset of use‐dependent block during repetitive activity and the slow offset kinetics of use‐dependent V max block suggest that E‐3753 exhibits class Ic antiarrhythmic actions in ventricular muscle fibres but does not exhibit class IV (Ca antagonist) antiarrhythmic actions.