EFFECTS OF BISARAMIL, A NOVEL CLASS-I ANTIARRHYTHMIC AGENT, ON HEART,SKELETAL-MUSCLE AND BRAIN NA+ CHANNELS

The effects of bisaramil, a novel diazabicyclononane antiarrhythmic ag ent, were compared to those of lidocaine, a clinically used class Ib a ntiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels expressed in Xenopus laevis oocytes using a two-electrode voltage clam p. Both bisaramil and lidocaine produced a concentration-dependent ton ic block of Na+ current that was most effective on cardiac channels, b ut bisaramil was more potent than Lidocaine. Both drugs produced a con centration-dependent shift in the voltage-dependence of inactivation a nd delayed recovery from inactivation. Bisaramil produced marked frequ ency-dependent block of heart channels and mild frequency-dependent bl ock of skeletal muscle and brain channels, whereas lidocaine produced marked frequency-dependent block of all three channel types. Therefore , bisaramil shows tonic and frequency-dependent blockade that is most potent against the heart Na+ channel, which may account for its potent antiarrhythmic efficacy in vivo, and may result in reduced central ne rvous system toxicity compared to clinically used agents such as lidoc aine. (C) 1998 Elsevier Science B.V.