Reference

Structure-activity relationships among newer histamine H2-receptor antagonists

Structure-activity relationships among newer histamine H2-receptor antagonists. Buyniski, J. P.; Cavanagh, R. L.Several substances are used for example 51481-61-9 which is its cas registry number.; Pircio, A. W.; Algieri, A. A.; Crenshaw, R. R. (Pharm. Res. Dev. Div., Bristol-Myers Co., Syracuse, NY 13201, USA). Highlights Recept. Chem., Proc. Camerino Symp. Recent Adv. Recept. Chem., 2nd, Meeting Date 1983, 195-215. Edited by: Melchiorre, Carlo; Giannella, Mario. Elsevier: Amsterdam, Neth. (English) 1984. CODEN: 52APAM. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacology) Cimetidine [51481-61-9], etintidine [69539-53-3], ranitidine [66357-35-5], famotidine (YM-11170) [76824-35-6], and BMY-25271 (3-amino-4-{2-[(5-dimelthylaminomethyl-2-furyl)methylthio]ethylamino}-1 ,2,5-thiadiazole 1-oxide) [78441-82-4] are thought to belong to a single homogeneous class of histamine [51-45-6] H2-receptor antagonists. In the dimaprit [65119-89-3]-stimulated isolated guinea pig right atrial prepn., the dissocn. consts. (Kb) for the antagonists relative to the pos. chronotropic effect of dimaprit were 0.41, 0.12, 0.16, 0.011, and 0.022 mM, resp. Each of the above H2-receptor antagonists acted as a competitive antagonist, the effect was readily reversible, and the compds. were readily washed out by changing the bath fluid. Similarly, all of the above compds. at equieffective in vivo oral doses have the same time response relation for inhibiting histamine-stimulated gastric acid secretion in the Heidenhain pouch dog. Receptor-site occupancy was used to identify chem. features in newly synthesized H2-receptor antagonists that would produce insurmountable antagonism and(or) bind tightly to the H2-receptor. Novel prototype compds. which have been identified include: BL-6341 (3-amino-4-{2-[(2-guanidinothiazol-4-yl)methylthio]ethylamino}-1,2,5-thi adiazole 1-oxide) [78441-84-6]; BMY-25368 (1-amino-2-[3-(3-piperidinomethylphenoxy)propylamino]-1-cyclobutene- 3,4-dione) [86134-80-7]; and BMY-25405 (3-amino-4-{3-[3-(piperidinomethyl)phenoxy]propylamino}-1,2,5-thiadia zole) [89077-71-4]. In the guinea pig right atrial prepn., the Kb values for the H2-receptor were 0.01, 0.013, and 0.003 mM, resp. Although BL-6341 and BMY-25405 showed a reversible assocn. complex with the receptors, washout expts. showed tighter binding to the H2 receptor as compared with cimetidine, ranitidine and famotidine. In contrast, BMY-25368 caused insurmountable antagonism and was not easily dissocd. from the receptor. Receptor protection studies with ranitidine have shown BMY-25368 to bind to the same population of H2-receptors as ranitidine, and also that the b-adrenergic receptor of the guinea pig right atrium is unaffected by BMY-25368. This latter information suggests that BMY-25368 does not produce true noncompetitive antagonism. In contrast to cimetidine, etintidine, ranitidine, BMY-25271, famotidine and oxmetidine [72830-39-8], BL-6341, BMY-25405, and BMY-25368 produce a prolonged oral gastric antisecretory effect in the Heidenhain pouch dog. Structure-activity relations of a no. of other H2-receptor antagonists are discussed and their activity profiles placed in perspective with the above described classes. .

Simultaneous analysis of cimetidine and ranitidine in human plasma by HPLC

Simultaneous analysis of cimetidine and ranitidine in human plasma by HPLC. Boutagy, J.; More, D. G.; Munro, I. A.; Shenfield, G. M. (Dep. Clin. Pharmacol., R. North Shore Hosp., St. Leonards 2065, Australia). J. Liq. Chromatogr., 7(8), 1651-64 (English) 1984. CODEN: JLCHD8. ISSN: 0148-3919. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A rapid method for the simultaneous quantitation of cimetidine [51481-61-9] and ranitidine [66357-35-5] in human plasma by isocratic ion-pair reverse-phase HPLC is described. A simple org. extn. step of the alkalinized plasma contg. added internal std. is followed by back extn. of the ext. with dil. AcOH and subsequent anal. of the aq. acidic phase on a reverse-phase (C18) column. The eluting solvent is MeCN-H2O () contg. 0.0005 mol/L octanesulfonic acid and is monitored at 229 nm. The run time for the assay is 12.5 min, with a detection limit for cimetidine of 50 ng/mL/(0.2 mmole/L) and that for ranitidine of 20 ng/mL (0.06 mmole/L).