Tolterodine is a new, potent and competitive
muscarinic receptor antagonist in clinical development for the treatment of
urge incontinence and other symptoms of unstable bladder.
Tolterodine has a high affinity and specificity for
muscarinic receptors in vitro and it exhibits a selectivity for the urinary bladder over salivary glands in vivo. A major active metabolite, (PNU-200577) the 5-hydroxymethyl derivative of
tolterodine, has a similar pharmacological profile. Based on pharmacological and pharmacokinetic data, it has been concluded that this metabolite contributes significantly to the
therapeutic effect of
tolterodine. The bladder selectivity demonstrated by
tolterodine and
PNU-200577 in vivo cannot be attributed to selectivity for a single
muscarinic receptor subtype. Moreover, this favourable tissue-selectivity seems to occur also in humans.
Tolterodine is well tolerated and it exerts a marked effect on bladder function in healthy volunteers. Phase II data indicate that
tolterodine is an efficacious and safe treatment for patients with idiopathic detrusor instability or detrusor
hyperreflexia. An optimal efficacy/side-effect profile is obtained with
tolterodine, at a dosage of 1 or 2 mg twice daily, which seems to have less propensity to cause dry mouth than the currently available
antimuscarinic drugs.