Bethanechol (DB01019): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Bethanechol is a synthetic choline ester classified as a direct-acting parasympathomimetic agent. It functions as a selective muscarinic receptor agonist, mimicking the effects of the endogenous neurotransmitter acetylcholine on target organs. Synthesized in 1935, bethanechol's therapeutic utility is predicated on two key molecular features: its high affinity for muscarinic receptors with negligible activity at nicotinic receptors, and its structural resistance to hydrolysis by cholinesterase enzymes.[1] This resistance confers a significantly longer duration of action compared to acetylcholine, making it a viable therapeutic agent.

The primary mechanism of action involves the stimulation of postganglionic muscarinic receptors, particularly the M3 subtype located on the smooth muscle of the urinary bladder and gastrointestinal tract.[3] This action increases the tone of the detrusor muscle, promoting bladder contraction and micturition, and enhances gastrointestinal motility. Consequently, bethanechol holds FDA approval for the treatment of acute postoperative and postpartum non-obstructive urinary retention, as well as for neurogenic atony of the bladder with retention.[5] Its pro-motility effects also support its off-label use in conditions such as gastroesophageal reflux disease (GERD).[8]