Effect of 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1 H-imidazo(4,5 h))isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimental cardiac arrhythmias in dogs.

Abstract

The effects of intravenously administered 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1H-imidazo (4,5H))-isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimentally induced ventricular tachycardia were studied in dogs. Ventricular tachycardia was produced in 6 anaesthetised dogs by the intravenous injection of ouabain (66.7 +/- 4.9 mg/kg). AR-LH31 administered by increasing bolus injections every 5 min completely suppressed the ventricular tachycardia with a return to sinus rhythm in 1 out of 6 dogs, with a partial return of sinus beats in a second dog. There was no return to sinus rhythm in the 4 remaining dogs after doses ranging from 1.75 to 15.75 mg/kg. Observations were made in 9 conscious dogs 22-24 hours after ligation of the anterior descending branch of the left coronary artery when a ventricular tachycardia was present. The administration of AR-LH31 by bolus intravenous injection in 4 dogs did not abolish the arrhythmia in any dog but increased the number of sinus beats. In 3 out of 4 dogs after a cumulative dose of 7.75 mg/kg, 60% of ventricular beats were of sinus origin. The effects of larger doses could not be studied be cause of adverse effects. In 5 dogs the administration of AR-LH31 by constant intravenous infusion at 16 mg/kg/h restored sinus rhythm in all dogs after a mean dose of 9.9 +/- 0.9 mg/kg. These studies indicate that AR-LH31 has anti-arrhythmic activity in dogs and highlight the importance of the method of administration in determining the effects of a drug.

• Authors: M J Kerr, D W Harron, R Wilson, R G Shanks
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 35 Issue 1A Pg. 197-200 ( 1985) ISSN: 0004-4172 [Print] Germany
• PMID: 3838674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Isoquinolines
• Ouabain
• AR-LH31

Topics

• Animals
• Anti-Arrhythmia Agents (therapeutic use)
• Coronary Vessels (physiology)
• Dogs
• Isoquinolines (therapeutic use)
• Ouabain
• Tachycardia (chemically induced, drug therapy, etiology)