Protective effects of felodipine and verapamil against imipramine-induced lethal cardiac conduction disturbances in the anaesthetized rat.
The effect of verapamil and felodipine on imipramine-induced cardiac toxicity was assessed in anaesthetized rats. Rats received either infusion of saline (n = 13), or non-hypotensive doses of felodipine (n = 36) or verapamil (n = 36) over 40 minutes. In saline-pretreated rats IV bolus injection of imipramine (10 mg/kg) resulted in severe hypotension, bradycardia, electromechanical dissociation, and death within 3 minutes. Rats pretreated with nonhypotensive doses of felodipine (1, 3, 6, and 10 micrograms/kg/min) or verapamil (10, 30, 100, and 300 micrograms/kg/min) survived throughout the experiment, despite an initial fall in blood pressure within the first 5 minutes after imipramine administration. Blood pressure returned to baseline levels within 15 minutes. Intermittent ECG monitoring showed significant prolongation of QRS duration after imipramine in both saline (by 138%) and verapamil-pretreated rats (by 63%), whereas in the rats pretreated with felodipine no prolongation was observed (+3%). We conclude that, in our experimental model, felodipine, more than verapamil, protects against the cardiac effects of imipramine intoxication.
Schoors
D F
DF
Department of Pharmacology, Vrije Universiteit Brussel (VUB), Belgium.
Reynaert
H
H
Huyghens
L
L
Vanhaelst
L
L
Dupont
A G
AG
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015736:Felodipine / Q000494:pharmacology*; D006329:Heart Conduction System / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007099:Imipramine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D014700:Verapamil / Q000494:pharmacology*
D014700:Verapamil; D007099:Imipramine; D015736:Felodipine