Local Effects of Antimuscarinics on Muscarinic Receptors in Bladder Sensory Nerves

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.

Antihistaminic efficacy of Ranitidine with & without Dimethendine maleate on histamine-induced cutaneous reactions.

The effect of Ranitidine, the H2-receptor antagonist, was investigated on cutaneous response to intradermal injection of histamine in healthy volunteers in a controlled, randomized, cross over study. The response was compared with that of the H1-receptor blocker; Dimethendine maleate used alone and in combination with the two antagonists. Reduction in the wheal area was significant in subjects pretreated with Ranitidine alone (P less than 0.05), and Dimethendine maleate alone (P less than 0.05); the combination of the two antagonists, did not produce additional reduction. Reduction in erythema area was not significant with Dimethendine maleate alone, but significant with Ranitidine alone (P less than 0.01). With the combination of the two antagonists the reduction was not more significant than with Ranitidine alone. The flare response scoring on visual analogue scale was not reduced significantly by Dimethendine maleate alone but reduced significantly by Ranitidine alone (P less than 0.10), and by combination of Ranitidine and Dimethendine maleate (P less than 0.05). Thus, Ranitidine appears to be more effective than Dimethendine maleate in reducing the erythema area and intensity of flare response and equieffective in reducing wheal response to histamine injection.