Bay k 8644, a calcium entry promoter, as an antidote in verapamil intoxication in rabbits.

The effects of the Ca++-entry promoters Bay k 8644 and CGP 28932 were compared with that of the potassium channel blocker 4-aminopyridine (4-AP) in urethane/chloralose anaesthetized rabbits subjected to a severe verapamil overdose. Heart rate (HR), blood pressure, E.C.G., acid-base status and plasma verapamil level were monitored. Intoxication was provoked upon i.a. infusion of verapamil, and resulted in complete atrioventricular (AV) dissociation and reduction of mean arterial pressure (MAP) by 55.6 +/- 2.0% (mean +/- S.E.M., n = 25). One minute after complete AV-dissociation, verapamil infusion was interrupted. Subsequently, treatment was started with an i.a. infusion of either Bay k 8644, CGP 28932 or 4-AP, whereas a control group was left untreated. The effects of treatment were assessed at 15 and 30 min after cessation of the verapamil infusion. The criteria were reversal of AV dissociation, and recovery of HR and MAP (HR, MAP greater than 65% of initial value). With the calcium entry promoter Bay k 8644 satisfactory protection against the deleterious symptoms of verapamil intoxication could be obtained. With respect to antidotal potency the following rank order was observed: Bay k 8644 much greater than CGP 28932 greater than 4-AP.