Possible mechanisms of anti-cholinergic drug-induced bradycardia

Summary 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.