Ameliorating effects of cloperastine on dysfunction of the urinary bladder caused by cerebral infarction in conscious rats.
We investigated the effects of the centrally acting antitussives dextromethorphan and cloperastine on urinary bladder dysfunction 24 h after cerebral infarction in rats using the cystometry technique. First, cystometrography was performed in conscious male Sprague-Dawley rats. Cerebral infarction was then induced by occlusion of the left middle cerebral artery. Twenty-four hours after cerebral infarction, the effect of each drug on micturition disorder was estimated for 5 parameters: bladder capacity, maximum voiding pressure, micturition latency, flow rate, and urethral resistance. Cerebral infarction markedly reduced bladder capacity, micturition latency, and flow rate and increased urethral resistance. After cerebral infarction, intravenous dosing of saline had no effect on these parameters. Dextromethorphan (20 mg/kg) and cloperastine (2.5 and 5.0 mg/kg) at antitussive effective doses significantly increased bladder capacity and micturition latency. Unlike dextromethorphan, cloperastine ameliorated decreases in flow rate and increases in urethral resistance caused by cerebral infarction. These results suggest that cloperastine may have therapeutic value for the treatment of disorders of the micturition reflex associated with cerebral infarction, and that the drug may become a base compound from which to develop more active drugs for such disorders.
Yamamoto
Gen
G
Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Soeda
Fumio
F
Shirasaki
Tetsuya
T
Takahama
Kazuo
K
D000818:Animals; D000996:Antitussive Agents / Q000627:therapeutic use*; D001259:Ataxia / Q000188:drug therapy / Q000209:etiology; D003915:Dextromethorphan / Q000627:therapeutic use*; D003950:Diagnostic Techniques, Urological; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000503:physiopathology; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology; D014554:Urination / Q000187:drug effects
D000996:Antitussive Agents; D010880:Piperidines; C040282:cloperastine; D003915:Dextromethorphan