title: Imidafenacin has no influence on learning in nucleus basalis of Meynert-lesioned rats.
abstract: The prevalence of overactive bladder (OAB) and Alzheimer's disease (AD) increases with age, and much attention has been paid to the risk of cognitive impairment which may be induced by antimuscarinics used for OAB in patients with AD. Imidafenacin, an antimuscarinic agent for OAB treatment, has been reported not to affect learning in normal animals. However, under the condition in which sensitivity to learning impairment by antimuscarinics is increased, it remains unclear whether imidafenacin still does not impair the learning. Therefore, the influences of imidafenacin on passive avoidance response were investigated in sham-operated and nucleus basalis of Meynert (nbM)-lesioned rats and compared with oxybutynin hydrochloride and tolterodine tartrate. The learning-inhibitory doses of intravenous oxybutynin hydrochloride and tolterodine tartrate were 0.3 and 3 mg/kg in sham-operated rats and 0.1 and 1 mg/kg in nbM-lesioned rats, respectively. Thus, the learning impairments by those antimuscarinics were more sensitive in nbM-lesioned rats than in sham-operated rats. On the other hand, intravenous administration of imidafenacin had no influence on learning in either case of the rats. In normal rats, however, intracerebroventricular administration of imidafenacin impaired learning to the same degree as that of oxybutynin hydrochloride. Thus, the present study suggests that imidafenacin, unlike the other antimuscarinics used, has no significant risk of enhancing learning impairment even in models whose sensitivity to learning impairment by antimuscarinics is commonly increased, probably because of its low brain penetration.
authors.affiliation: Development Research Laboratories, Kyorin Pharmaceutical Co., Ltd., 1848, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi, 329-0114, Japan, takanobu.yamazaki@mb.kyorin-pharm.co.jp.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Ayako
authors.initials: A
authors.lastname: Fukata
mesh_terms: D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000378:metabolism; D002199:Capillary Permeability; D003408:Cresols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects*; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010665:Phenylpropanolamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D000068737:Tolterodine Tartrate
chemical_list: D001559:Benzhydryl Compounds; D003408:Cresols; D007093:Imidazoles; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C005419:oxybutynin; C120953:imidafenacin