Effects of the optical isomers of verapamil on electrophysiological properties of the heart in conscious dogs.
We compared the cumulative dose-response relations of verapamil (0.1, 0.2 and 0.4 mg kg(-1)) in different R/S enantiomer ratios (100/0, 90/10, 80/20, 50/50 and 20/80) on the electrophysiological and hemodynamic characteristics of the heart using the conscious dogs. A reduction of mean arterial pressure occurred with 20R/80S producing a 3-times greater decrease than 100R/0S, but an increase in heart rate occurred with 20R/80S producing a 9-times greater increase than 100R/0S. Increased heart rate was concurrent with decreased mean arterial pressure most prevalent with a higher ratio of S-isomer that produced a greater reduction in mean arterial pressure and increase in heart rate at lower overall verapamil doses. Atrio-ventricular conduction time increased 3-5 min after each infusion, with 20R/80S producing a 4-times greater effect than 100R/0S. These results indicate that the peripheral and cardiac electrophysiologic properties of various nonracemic verapamil mixtures are mainly attributable to the concentration of S-isomer.
Takahata
O
O
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Krolikowski
J G
JG
McCallum
J B
JB
Lathrop
D A
DA
Bosnjak
Z J
ZJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D014700:Verapamil