Abstract
Aniracetam has been used to improve the mental condition of patients with cerebrovascular disease. Previous studies have demonstrated that aniracetam activates the residual functions of cholinergic neurons in damaged brain areas. In this study, the effects of aniracetam on bladder overactivity after left middle cerebral artery occlusion were assessed through oral or i.c.v. administration in sham-operated and cerebral infarcted rats. Oral administration of aniracetam (100 and 300 mg/kg) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but had no effect on bladder capacity in sham-operated rats. Intracerebroventricular administration of aniracetam (0.25 and 2.5 μg/rat) resulted in a significant and dose-dependent increase in bladder capacity in cerebral infarcted rats but not in sham-operated rats. Aniracetam had no significant effect on bladder contraction pressure or micturition threshold pressure in either sham-operated or cerebral infarcted rats. Furthermore, i.c.v. administration of atropine (1 μg/rat), a muscarinic acetylcholine receptor antagonist, completely inhibited the enhancing effects of aniracetam on bladder capacity in cerebral infarcted rats. The effects of aniracetam on bladder overactivity are thought to be mediated in part by activation of cholinergic inhibitory mechanisms in the brain. These results indicate that aniracetam may improve the neurogenic voiding dysfunction observed in patients with cerebrovascular disease.
Footnotes
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Send reprint requests to: Yasushi Nakada, Dept. of Urology, Kanazawa University School of Medicine, 13-1 Takara-machi Kanazawa Ishikawa 920-8641 Japan. E-mail: yasushi_nakada{at}toyama-chemical.co.jp
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↵1 Present address: Research Laboratories, Toyama Chemical Co. Ltd., Toyama 930-8508, Japan.
- Abbreviations:
- PMC
- pontine micturition center
- aCSF
- artificial cerebrospinal fluid
- AMPA/KA
- α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate
- CMG
- cystometrography
- ICA
- internal carotid artery
- ACh
- acetylcholine
- mAChR
- muscarinic acetylcholine receptor
- MCA
- middle cerebral artery
- rCBF
- regional cerebral blood flow
- Received November 29, 1999.
- Accepted February 8, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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