title: Effects of bisaramil, a novel class I antiarrhythmic agent, on heart, skeletal muscle and brain Na+ channels.
abstract: 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 Na+ channels expressed in Xenopus laevis oocytes using a two-electrode voltage clamp. Both bisaramil and lidocaine produced a concentration-dependent tonic block of Na+ 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-dependence 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-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 nervous system toxicity compared to clinically used agents such as lidocaine.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine 92697-4025, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Pugsley
authors.forename: A L
authors.initials: AL
authors.lastname: Goldin
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002722:Chlorobenzenes; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014981:Xenopus
chemical_list: D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002722:Chlorobenzenes; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D008012:Lidocaine; C045644:bisaramil