Effects of carbamazepine on the water permeability and short-circuit current of the urinary bladder of the toad and the response to vasopressin, adenosine 3',5'-cyclic phosphate and theophylline

KE Meier and SA Mendoza

Carbamazepine has been reported to decrease urine output and increase urinary concentration in patients with diabetes insipidus. The effects of the drug on the osmotic water permeability of the bladder of the toad, Bufo marinus, were studied. Carbamazepine had no effect on osmotic water flow when present in the serosal or mucosal bathing media. The submaximal or maximal increase in osmotic water flow caused by vasopressin was inhibited by serosal carbamazepine concentrations as low as 0.01 mM. Higher concentrations of carbamazepine in the mucosal solution also inhibited the submaximal antidiuretic hormone (ADH) response. The response to 2 mM cyclic AMP was inhibited by 0.5 mM serosal carbamazepine. Carbamazepine did not affect the response to 20 mM theophylline. Significant inhibition of the ADH response occurred only after preincubation of the bladders with the drug for at least 1 hour. The inhibition was reversed by rinsing the drug from the bladders before ADH was added. The mechanism of action of carbamazepine in diabetes insipidus remains obscure. In the toad bladder, the drug neither directly increases osmotic water flow nor potentiates the response to vasopressin.

Volume 200, Issue 1, pp. 95-100, 01/01/1977
Copyright © 1977 by American Society for Pharmacology and Experimental Therapeutics