Effect of antimuscarinic drugs used for overactive bladder on learning in a rat passive avoidance response test.
Antimuscarinic drugs are used for the treatment of overactive bladder. One adverse effect associated with their use, however, is cognitive impairment arising from their anticholinergic action. Here, we examined the effects of antimuscarinic drugs on learning using a passive avoidance task in rats. Drugs were intravenously administered 10 min before an acquisition trial, followed 24 h later by measurement of latency time in the passive avoidance task in a retention trial. Oxybutynin (0.1-1 mg/kg i.v.), propiverine (1-10 mg/kg i.v.) and scopolamine (0.1-1 mg/kg i.v.) impaired learning at doses of 0.3 mg/kg i.v. or more, 10 mg/kg i.v., and 0.3 mg/kg i.v. or more, respectively. Tolterodine (0.1-1 mg/kg i.v.) tended to impair these functions at a dose of 1 mg/kg i.v. In contrast, darifenacin (0.1-1 mg/kg i.v.) and solifenacin (0.3-3 mg/kg i.v.) showed no impairment of these functions. We also examined the effects of antimuscarinic drugs on learning enhanced by the cholinesterase inhibitor donepezil at a dose of 0.1 mg/kg i.v. in scopolamine-treated rats. Oxybutynin (0.1-1 mg/kg i.v.) impaired these donepezil-enhanced functions, whereas solifenacin (0.3-3 mg/kg i.v.) produced no significant impairment. These results suggest that antimuscarinic drugs such as darifenacin, solifenacin and tolterodine may have less effect on cognitive function in the treatment of patients with overactive bladder.
Suzuki
Masanori
M
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585 Japan. masamori-suzuki@jp.astellas.com
Noguchi
Yukiko
Y
Okutsu
Hiroko
H
Ohtake
Akiyoshi
A
Sasamata
Masao
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D007858:Learning / Q000187:drug effects*; D008297:Male; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D053201:Urinary Bladder, Overactive / Q000188:drug therapy*
D018727:Muscarinic Antagonists