Detail of "76963-41-2"

Reference

Effect of five structurally diverse H2-receptor antagonists on drug metabolism

Effect of five structurally diverse H2-receptor antagonists on drug metabolism. Pasanen, Markku; Arvela, Pentti; Pelkonen, Olavi; Sotaniemi, Eero; Klotz, Ulrich (Dep. Pharmacol., Univ. Oulu, Oulu SF-90220, Finland). Biochem. Pharmacol., 35(24), 4457-61 (English) 1986. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Some H2-receptor antagonists can interact with the biotransformation of other drugs. This is due to their binding to cytochrome P 450 [9035-51-2]. The in vitro effects of 5 different H2-receptor antagonists, cimetidine (C) [51481-61-9], oxmetidine (O) [72830-39-8], ranitidine (R) [66357-35-5], famotidine (F) [76824-35-6], and nizatidine (N) [76963-41-2] on arylhydrocarbon hydroxylase [9037-52-9], 7-ethoxycoumarin O-deethylase [42613-26-3], and 7-ethoxyresorufin O-deethylase [59793-97-4] activity were tested by use of liver microsomes from man as well as from untreated, phenobarbital and 3-methylcholanthrene treated rats. In addn. their binding to human microsomal cytochrome P 450 was evaluated. The in vivo effects of these antagonists were investigated on the hepatic elimination of diazepam [439-14-5] in healthy volunteers. In vitro O was found to be the most effective inhibitor of the enzyme activities studied. C showed a clear inhibitory effect only with rat liver microsomes, whereas the remaining drugs were more than 10 times less potent. The binding affinities of these antagonists showed a similar tendency: the Ks-values for O, C and R were 0.2, 0.9 and 5.1 mM, resp.; for F and No no binding up to 4 mM could be obsd. However, in man, only C inhibited the hepatic elimination of diazepam by about 45% while R, O, N, and F did not affect the pharmacokinetics of diazepam. Thus, it could be concluded that one cannot extrapolate in vitro data of the inhibitory potency of H2-receptor antagonists in every case to human in vivo drug metab.

Nocturnal acid suppression with a new H2 receptor antagonist - nizatidine

Nocturnal acid suppression with a new H2 receptor antagonist - nizatidine.Some chemicals with cas registry numbers like 12408-02-5 and 66357-35-5 are also used. Dammann, H. G.; Gottlieb, W. R.; Walter, T. A.; Dreyer, M.; Mueller, P.; Simon, B.; Keohane, P. (Krankenhaus Bethanien Hamburg, Hamburg 2000/20, Fed. Rep. Ger.). Hepato-Gastroenterology, 33(5), 217-20 (English) 1986. CODEN: HEGAD4. ISSN: 0172-6390. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) To det. the potential efficacy of bedtime doses of the new furan H2 receptor antagonist nizatidine (I) [76963-41-2] in the suppression of nocturnal acid secretion, this randomized, crossover, single-blind study was performed in 10 healthy male subjects. The actions of a single bedtime (21.00 h) dose of the H2 receptor antagonists nizatidine (150 mg and 300 mg), ranitidine [66357-35-5] (300 mg) and cimetidine [51481-61-9] (800 mg), as well as placebo on nocturnal gastric acid and vol. secretion (01.00 to 07.00 h) and on overall 24 h H+ ion concn. were studied. Compared with placebo, night-time (23.00 to 07.00 h) H+ ion concn. was reduced by 70, 79, 95, and 76%. Nocturnal acid secretion, too, was lower for the H2 blockers than for placebo. A redn. in night-time gastric vol. secretion was obsd. in the hourly intervals from 04.00 to 07.00 h and in total vol. in the whole 6 h period. Nizatidine 300 mg at night, ranitidine, and cimetidine decreased H+ concn. for only 1 h (08.00 to 09.00 h) during the subsequent daytime period (08.00 to 13.00 h). Since no significant pharmacodynamic differences between nizatidine 300 mg at night, cimetidine 800 mg at night and ranitidine 300 mg at night were obsd., it may be concluded that at the doses employed, these three H2-blockers will all be similarly effective in the acute therapy of peptic ulcer disease. .