Effect of PK11195 on cardiovascular toxicity due to verapamil: an experimental study in the dog

In vitro studies have suggested that peripheral binding sites (PBR) for benzodiazepine (BZD) could be coupled to the voltage operated calcium channel (VOC) in the heart and that PK11195, an non-BZD ligand with antagonistic activity at this receptors, could inhibit the electrophysiological and mechanical properties of both "peripheral" benzodiazepines and calcium channel blockers. This study evaluates the antidotal value of PK11195 against the cardiovascular depression and arrhythmias in a canine model of acute verapamil intoxication. Although sinus activity is more often preserved or restored (7/8 vs 1/6) in the animals treated with PK11195, this compound, administered in doses able to saturate heart PBR, is unable to prevent or correct the haemodynamic alterations induced by acute verapamil intoxication and the improvement of survival (8/8 vs 3/6) is not significant.