PMID: 6156339Jul 1, 1980

The effects of prolonged oral administration of a new antidysrhythmic drug (Org 6001) on coronary artery ligation dysrhythmias in conscious and anesthetized rats

Journal of Cardiovascular Pharmacology
K KaneL Szekeres

Abstract

We determined the antidysrhythmic activity of acute or prolonged administration of Org 6001 on dysrhythmias following coronary artery ligation in conscious and anesthetized rats. Intravenous doses of 5 and 10 mg/kg of Org 6001 markedly protected against postligation dysrhythmias in anesthetized rats, whereas a single oral dose of 10 mg/kg given 1 hr prior to ligation did not. Prolonged oral administration of Org 6001, 10 mg/kg twice daily for 10 days, the last dose given 1 hr before ligation, reduced the incidence of ventricular fibrillation and increased survival in both conscious and anesthetized animals. This effective antidysrhythmic dose regimen resulted in drug concentrations of 335 +/- 68 ng/ml in plasma and 2,940 +/- 408 ng Org 6001/g in the whole heart. At 24 hr after the last dose no protection against the dysrhythmias remained, and drug levels in both plasma and heart tissue were low. A good correlation was observed between the levels of Org 6001 in the heart and the reduction in the rate of rise of phase zero of cardiac action potentials obtained from drug-pretreated animals. It is concluded that prolonged administration of Org 6001 is effective against postligation dysrhythmias and that this effect may be associate...Continue Reading

Citations

Nov 5, 1981·European Journal of Pharmacology·O Fagbemi, J R Parratt
May 30, 1989·European Journal of Pharmacology·R R BrooksC M Gregory
May 1, 1983·Journal of Pharmacological Methods·I LepránL Szekeres
Jan 1, 1984·Pharmacology & Therapeutics·E Winslow
Jan 1, 1981·General Pharmacology·R J Marshall, E Winslow
Aug 1, 1982·British Journal of Pharmacology·O FagbemiL Szekeres

Related Concepts

Org 6001
Androstanols
Anesthesia Procedures
Cardiac Depressants
Cardiac Arrhythmia
Sinus Node Artery
Electrophysiology (Science)
Intravenous Injections
Ligature

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