.European Journal of Pharmacology 342 1998 93–104 Effects of bisaramil, a novel class I antiarrhythmic agent, on heart, skeletal muscle and brain Naq channels

The effects of bisaramil, a novel diazabicyclononane antiarrhythmic agent, were compared to those of lidocaine, a clinically used class Ib antiarrhythmic agent, on heart, skeletal muscle and brain Naq channels expressed in Xenopus lae˝is oocytes using a two-electrode voltage clamp. Both bisaramil and lidocaine produced a concentration-dependent tonic block of Naq current that was most effective on cardiac channels, but bisaramil was more potent than lidocaine. Both drugs produced a concentration-dependent shift in the voltage-de-pendence of inactivation and delayed recovery from inactivation. Bisaramil produced marked frequency-dependent block of heart channels and mild frequency-dependent block of skeletal muscle and brain channels, whereas lidocaine produced marked frequency-de-pendent block of all three channel types. Therefore, bisaramil shows tonic and frequency-dependent blockade that is most potent against the heart Naq channel, which may account for its potent antiarrhythmic efficacy in vivo, and may result in reduced central nervous system toxicity compared to clinically used agents such as lidocaine. q 1998 Elsevier Science B.V