Atropine and verapamil interactions in healthy volunteers

The calcium antagonist falipamil, a chemical congener of verapamil, has anticholinergic properties. It was decided to study the interaction of verapamil with the anticholinergic drugs, atropine and pirenzepine, using healthy male volunteers. After atropine alone a significant tachycardia developed at 2 min and remained significant up to 90 min. Verapamil pretreatment followed by atropine administration resulted in a significantly greater tachycardia. Pirenzepine alone caused a bradycardic response which was accentuated after verapamil pretreatment. It is postulated that short term verapamil administration is accompanied by reflex activation of the sympathetic nervous system which does not manifest with a tachycardia owing to combined influence of verapamil and vagus on the sino-atrial node. Reduction of vagal tone with atropine treatment results in sympathetic overriding of the sino-atrial suppression, thus causing an additive tachycardia. The clinical use of atropine for prolonged verapamil-induced atrio-ventricular conduction is supported by these results.