TOLTERODINE - A NEW BLADDER SELECTIVE MUSCARINIC RECEPTOR ANTAGONIST - PRECLINICAL PHARMACOLOGICAL AND CLINICAL-DATA

Tolterodine is a new, potent and competitive muscarinic receptor antag onist in clinical development for the treatment of urge incontinence a nd other symptoms of unstable bladder. Tolterodine has a high affinity and specificity for muscarinic receptors in vitro and it exhibits a s electivity for the urinary bladder over salivary glands in vivo. A maj or active metabolite, (PNU-200577) the 5-hydroxymethyl derivative of t olterodine, has a similar pharmacological profile. Based on pharmacolo gical and pharmacokinetic data, it has been concluded that this metabo lite contributes significantly to the therapeutic effect of tolterodin e. The bladder selectivity demonstrated by tolterodine and PNU-200577 in vivo cannot be attributed to selectivity for a single muscarinic re ceptor subtype. Moreover, this favourable tissue-selectivity seems to occur also in humans. Tolterodine is well tolerated and it exerts a ma rked effect on bladder function in healthy volunteers. Phase II data i ndicate that tolterodine is an efficacious and safe treatment for pati ents with idiopathic detrusor instability or detrusor hyperreflexia. A n optimal efficacy/side-effect profile is obtained with tolterodine, a t a dosage of 1 or 2 mg twice daily, which seems to have less propensi ty to cause dry mouth than the currently available antimuscarinic drug s.