Possible mechanisms of anti-cholinergic drug-induced bradycardia

Atropine-induced bradycardia is traditionally ascribed to central vagal stimulation, although bradycardia has also been observed after administration of quarternary amines. Pirezepine, a selective M1-antagonist, causes bradycardia in therapeutic doses for which a peripheral mechanism is postulated. This hypothesis has been investigated in healthy volunteers. Atropine 0.5 mg caused significant bradycardia from 210 min and pirenzepine 10 mg after 60 min. After prior beta-blockade, the bradycardic action of the anti-cholinergic drugs was more marked. Pirenzepine-induced bradycardia was reversed by higher doses of atropine. It is suggested that atropine- and pirenzepine-induced bradycardia results from M1-blockade of sympathetic ganglia. In addition, low concentrations of atropine and therapeutic doses of pirenzepine may cause an increase in acetylcholine, perhaps due to a presynaptic effect on nerve endings.