Pfizer Global Research and Development, Groton, CT, United States

Antimuscarinics are first-line pharmacotherapy for the treatment of overactive bladder. However, because central nervous system cholinergic neurotransmission is involved in cognition, and the central nervous system-permeable antimuscarinics scopolamine and oxybutynin affect memory, cognitive impairment has been noted as a possible side effect of these drugs. We evaluated the effect of tolterodine, an antimuscarinic for overactive bladder, in a mouse passive-avoidance model of memory. Mice were chosen because like humans, mice but not rats, form the pharmacologically active 5-hydroxymethyl metabolite of tolterodine, DD01. In the passive-avoidance test, tolterodine at 1 or 3 mg/kg had no effect on memory; the latency to cross and percentage of animals crossing were comparable to controls. In contrast, scopolamine induced a memory deficit; the latency to cross was decreased, and the number of animals crossing was increased. Therefore, at a dose exceeding therapeutic exposure by six-fold, tolterodine had no effect on memory in the mouse passive-avoidance model, indicating that tolterodine does not disrupt cognitive function in this testing paradigm.

Written by
Cappon GD, Bush B, Newgreen D, Finch GL, Alper RH.

Reference
Eur J Pharmacol. 2007 Oct 30 [Epub ahead of print]
doi:10.1016/j.ejphar.2007.10.063

PubMed Abstract
PMID:18031724

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UroToday.com Overactive Bladder (OAB) Section

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