Studies on the protective effect of azepexole on ouabain-induced cardiac arrhythmias and lethality in guinea-pig.

Abstract

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.

• Authors: G P Thomas
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 276 Issue 3 Pg. 215-21 (Apr 04 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7541362 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Antagonists
• Anti-Arrhythmia Agents
• Azepines
• Dioxanes
• Yohimbine
• Ouabain
• Reserpine
• azepexole
• Idazoxan

Topics

• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Arrhythmias, Cardiac (chemically induced, physiopathology)
• Azepines (pharmacology)
• Blood Pressure (drug effects)
• Cardiac Complexes, Premature (chemically induced, prevention & control)
• Cardiac Pacing, Artificial
• Dioxanes (pharmacology)
• Female
• Guinea Pigs
• Heart Rate (drug effects)
• Idazoxan
• In Vitro Techniques
• Male
• Ouabain (antagonists & inhibitors, toxicity)
• Reserpine (pharmacology)
• Yohimbine (pharmacology)