The effects of bisaramil on experimental arrhythmias.
Antiarrhythmic activity of bisaramil (3-methyl,7-ethyl,9 alpha, 4'-(Cl-benzoyloxy)-3,7-diazabicyclo[3.3.1.]nonane monohydrochloride) was investigated in a variety of experimental arrhythmic models. Bisaramil at the dose range of 0.1-2 mg/kg given i.v. was able to protect against either chemically induced (chloroform, aconitine, adrenaline, ouabain) or coronary-ligation-induced arrhythmias. Bisaramil dose dependently increased fibrillation threshold both in the right auricle and in the right ventricle (ED50 approximately 0.2 mg/kg i.v.) and decreased the susceptibility of the heart to arrhythmias induced by programmed electrostimulation alone or together with local cooling of the heart. Bisaramil given orally (5-20 mg/kg) also showed antiarrhythmic activity with a medium (2-4 h) duration of the action. Therapeutic index of bisaramil was found to be 19.6 (rat); 5.0 (dog) by i.v. administration and 46.5 (rat); 15.5 (dog) by p.o. administration. This means that bisaramil may be given rather safely.
Paróczai
M
M
Pharmacological Research Centre, Chemical Works of Gedeon Richter Ltd, Budapest, Hungary.
Kárpáti
E
E
Solti
F
F
D000157:Aconitine; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use* / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use* / Q000633:toxicity; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D002415:Cats; D002722:Chlorobenzenes; D002725:Chloroform; D003080:Cold Temperature; D003331:Coronary Vessels / Q000502:physiology; D004285:Dogs; D004558:Electric Stimulation; D004837:Epinephrine; D005260:Female; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010042:Ouabain; D051381:Rats; D011919:Rats, Inbred Strains; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D002722:Chlorobenzenes; D010042:Ouabain; D002725:Chloroform; C045644:bisaramil; D000157:Aconitine; D004837:Epinephrine