Effects of antimuscarinic drugs on both urinary frequency and cognitive impairment in conscious, nonrestrained rats.
Recent studies indicate a risk of learning and memory impairments when patients with senile dementia are treated with antimuscarinic drugs. In this study, we compared the effectiveness of propiverine hydrochloride (propiverine) and oxybutynin chloride (oxybutynin) on the increased urinary frequency and cognitive impairment induced by nucleus basalis magnocellularis (nBM) lesioning in conscious and nonrestrained rats. For examination of bladder function, nBM-lesioned rats were given total parenteral nutrition regimens for 8 days. Propiverine administered orally at 0.3, 3 and 30 mg/kg on the postoperative day 7 significantly lessened the increase in the frequency of voiding caused by the nBM lesion, whereas oxybutynin administration did not show any improvement at 0.1 or 1 mg/kg but did so at 10 mg/kg. To examine the memory impairment, we trained nBM-lesioned rats in an 8-arm radial maze task for 20 days and then evaluated the effectiveness of oral drug administration on 19th and 20th radial maze performance. The higher rate of errors caused by nBM lesioning was significantly aggravated by oxybutynin at 30 and 100 mg/kg. Propiverine showed slight aggravation of errors, but with no statistical significance at any dose, 30, 100 or 300 mg/kg. These results suggest that propiverine has comparatively less effect on the cognitive impairment than oxybutynin.
Oka
T
T
Pharmacology Research Laboratory, Taiho Pharmaceutical Co., Ltd, Tokushima, Japan. t-oka@taiho.co.jp
Nakano
K
K
Kirimoto
T
T
Matsuura
N
N
D000284:Administration, Oral; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000293:injuries; D001561:Benzilates / Q000494:pharmacology* / Q000652:urine; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003243:Consciousness; D004195:Disease Models, Animal; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology* / Q000652:urine; D018782:Maze Learning / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000652:urine; D010276:Parasympatholytics / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology / Q000652:urine; D014549:Urinary Incontinence / Q000188:drug therapy; D014554:Urination / Q000187:drug effects
D001561:Benzilates; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; C015586:propiverine; D012601:Scopolamine; C005419:oxybutynin