title: Electrophysiological actions of a new antiarrhythmic drug, bisaramil, on isolated heart preparations.
abstract: Electrophysiological effects of bisaramil--a new antiarrhythmic drug under clinical trial--were investigated on isolated heart preparations, at a concentration range of 2.3-23 x 10(-6) M. Bisaramil dose dependently decreased the maximum rate of depolarization (Vmax), action potential amplitude (APA) and overshoot (OS) both in auricle and in papillary muscle of guinea-pig heart. There was no significant and obvious effect on the duration of the action potential and the resting membrane potential was also unchanged. Bisaramil slowed the spontaneous frequency of pacemaker cells in rabbit sinus node preparation due to its inhibitory effect on slow diastolic depolarization (SDD). Bisaramil was able to inhibit slow Ca(2+)-action potentials induced by isoprenaline on K(+)-depolarized papillary muscle. Results obtained with transmembrane current measurements revealed that bisaramil inhibited both fast Na(+)-current and slow Ca(2+)-current in frog sinoauricular fibres at the same concentration. Bisaramil with a mixed mode of the action seems to be a very promising drug.
authors.affiliation: Chemical Works of Gedeon Richter Ltd, Pharmacological Research Centre, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Paroczai
authors.forename: E
authors.initials: E
authors.lastname: Karpati
authors.forename: R
authors.initials: R
authors.lastname: Marko
authors.forename: V
authors.initials: V
authors.lastname: Kecskemeti
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002722:Chlorobenzenes; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D011893:Rana esculenta
chemical_list: D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002722:Chlorobenzenes; C045644:bisaramil