Effects of Antimuscarinic Drugs on Both Urinary Frequency and Cognitive Impairment in Conscious, Nonrestrained Rats

Abstract

ABSTRACT-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.Keywords: Antimuscarinic, Propiverine, Oxybutynin, Dementia, Urinary frequency Recently, the number of patients with abnormally high urinary frequency and/ or urinary incontinence attributed to neurogenic or unstable bladder has been increasing. In particular, the number of patients with neurogenic bladder that results from functional disturbance of the brain (for example, dementia and cerebrovascular disease) is expected to increase concomitantly with the aging of society and the increase in the frequency of traffic accidents. As urinary bladder contraction is controlled largely by parasympathetic nerves, a peripherally active anticholinergic (antimuscarinic) drug, for example, oxybutynin or propiverine (1, 2), is generally used for the treatment of urinary frequency and incontinence. On the other hand, scopolamine, a centrally active anticholinergic agent, has been found to create transient memory impairments more frequently in the Alzheimer-type dementia patients than in age-matched elderly control subjects (3 -5). Depending on the situation, antimuscarinic therapeutic drugs given for the treatment of increased urinary frequency and incontinence would also thus have the potential to create transient memory impairment in patients with senile dementia. However, there have been no clinical or animal studies reported to show whether these drugs affect the memory impairment in dementia or not.Furthermore, under conscious and nonrestrained conditions, there have been few animal studies that have examined the effects of antimuscarinic therapeutic drugs on urinary frequency. These conditions are considered to be essential to assess the clinical efficacy of ora...

Binding activities by propiverine and its N-oxide metabolites of L-type calcium channel antagonist receptors in the rat bladder and brain

“…Also, propiverine at the oral dose over 50 mg/kg inhibited performance of conditioned avoidance response in rats (Toide et al, 1989). Similarly, oral administration of this agent (30, 100 and 300 mg/ kg) showed slight aggravation of errors, with no statistical significance among these doses, in the cognitive impairment in the nucleus basalis magnocellularis (nBM)-lesioned rats as a cerebral dysfunction model (Oka et al, 2001). Therefore the extent of CNS effect by propiverine through the blockade of these receptors may be small under the in vivo condition.…”

Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: a prospective analysis

“…Serious adverse effects involving the CNS, e.g. hallucinations, drowsiness and cognitive impairment, can also occur [10,11] in children treated with oral and intravesical oxybutynin [8]. This is particularly important because the combined use of CIC with anticholinergics should be started in early childhood, preferably even in newborns [12,13].…”

Comparison of the Effects by Obybutynin and Tolterodine on Spina Bifida Patients: A Pilot Crossover Study

“…Consequently, each NGB patient responds differently to each anticholinergic drug, making an individualized approach mandatory for the choice of optimal drug. Further, we should note the mental disturbance caused by obybutynin due to the passage of the drug through the blood‐brain barrier 14,15 . In this study no marked difference in mental activity was noted in the enrolled patients.…”