Studies on the protective effect of azepexole on ouabain-induced cardiac arrhythmias and lethality in guinea-pig.
Azepexole, an alpha 2-adrenoceptor agonist (125, 250 and 500 micrograms/kg i.v.), was examined for its effect on ouabain-induced ventricular premature beats, ventricular tachyarrhythmias and lethality in guinea-pigs. The doses of ouabain required to cause ventricular arrhythmias and lethality were significantly higher in azepexole-treated animals. However, it did not offer any protection in reserpinised guinea-pigs. Idazoxan, the alpha 2-adrenoceptor antagonist (100 micrograms/kg i.v.) inhibited the protective action of azepexole while corynanthine, the alpha 1-adrenoceptor antagonist (1 mg/kg i.v.), potentiated the effect. Azepexole inhibited the rate of the ouabain-induced rise in mean arterial blood pressure and the peak pressor response. In isolated paced left atria of guinea-pig, azepexole (2.76 x 10(-3) M) did not offer any protection against extrasystolic contractions induced by ouabain. Therefore the protective effect of azepexole may be mediated through the stimulation of alpha 2-adrenoceptors and the resultant suppression of the indirect neural components of ouabain toxicity.
Thomas
G P
GP
Department of Pharmacology, IDPL Research Centre, Hyderabad, India.
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D001381:Azepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005117:Cardiac Complexes, Premature / Q000139:chemically induced / Q000517:prevention & control; D002304:Cardiac Pacing, Artificial; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D012110:Reserpine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000889:Anti-Arrhythmia Agents; D001381:Azepines; D004146:Dioxanes; D015016:Yohimbine; D010042:Ouabain; D012110:Reserpine; C015603:azepexole; D019329:Idazoxan