Local Effects of Antimuscarinics on Muscarinic Receptors in Bladder Sensory Nerves

ABSTRACT

PURPOSE: To investigate the role of muscarinic receptors in bladder sensory mechanism. MATERIALS AND METHODS: Normal adult volunteers collected voided urine after taking five days of trospium(20 mg bid), tolterodine LA(4 mg qd) and oxybutynin XL(10 mg qd). The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats. Cystometric parameters during continuous infusion for over one hour each of saline, human urine, then mixture of carbachol and human urine were compared(n=6 in each group). Then 0.1 and 0.5microgram/ml of oxybutynin, trospium, tolerodine, and dimethindene were studied with the same methods. RESULTS: Human urine with or without intake of antimuscarinic agents had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after an addition of carbachol to human urine containing vehicle, tolterodine or oxybutynin. Human urine after ingestion of trospium, however, prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case. 0.1 and 0.5microgram/ml of oxybutynin, trospium, tolerodine, and dimethindene prevented the decrease of intercontraction interval with intravesical carbachol(65+/-0.1% compared with baseline). CONCLUSION: The excreted urine after oral ingestion of 20 mg bid of trospium has a significant inhibitory effect in a rat model of detrusor overactivity. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating bladder overactivity, not only by suppression of muscarinic receptor-mediated detrusor muscle contraction, but also by blocking muscarinic receptors in bladder-afferent pathways.