Tolterodine (DB01036): A Comprehensive Pharmacological and Clinical Monograph

I. Executive Summary

Tolterodine is a potent and competitive muscarinic receptor antagonist, pharmacologically classified as a urinary antispasmodic agent. It was specifically developed for the symptomatic management of overactive bladder (OAB), a condition characterized by urinary urgency, frequency, and urge incontinence.[1] The therapeutic rationale for Tolterodine is based on its ability to antagonize M2 and M3 muscarinic receptor subtypes, which are densely expressed in the detrusor smooth muscle of the urinary bladder. This antagonism inhibits acetylcholine-mediated involuntary bladder contractions, leading to a reduction in intravesical pressure, an increase in bladder capacity, and alleviation of OAB symptoms.[3]

A defining characteristic of Tolterodine's pharmacology is the pivotal role of its primary active metabolite, 5-hydroxymethyltolterodine (5-HMT). Following oral administration, Tolterodine undergoes extensive hepatic metabolism, and the resulting 5-HMT possesses an antimuscarinic activity profile that is equipotent to the parent compound, contributing substantially to the overall therapeutic effect.[6] This dual contribution from both the parent drug and its active metabolite is a central feature of its clinical profile.

Clinically, Tolterodine has demonstrated robust efficacy superior to placebo and comparable to the older benchmark agent, oxybutynin, in reducing micturition frequency and incontinence episodes in patients with OAB.[3] The subsequent development and approval of an extended-release (ER) formulation represented a significant therapeutic advance, offering improved efficacy and a more favorable tolerability profile compared to the immediate-release (IR) version by mitigating peak-concentration-related side effects.[11]