H2 -histamine receptor antagonists

Histamine H2 Receptor Antagonists. In 1972 a new class of histamine antagonists was described that was capable of antagonizing histamine-induced gastric acid secretion (6). The H2 antagonists are divided into five stmctural classes, some of which are shown in Table 3. A more complete review can be found in Reference 25. 

The principal OTC pharmaceutical products include cold remedies, vitamins and mineral preparations, antacids, analgesics, topical antibiotics, antiftingals and antiseptics, and laxatives. Others include suntan products, ophthalmic solutions, hemorrhoidal products, sleep aids, and dermatological products for treatment of acne, dandmff, insect parasites, bums, dry skin, warts, and foot care products (11). More recent prescription-to-OTC switches have included hydrocortisone, antihistamine and decongestant products, antiftingal agents, and, as of 1995, several histamine H2-receptor antagonists. 

From 1981 to 1995 other dmgs switched to OTC were the antifiingal preparations containing micona2ole nitrate [22832-87-7] (7) and clotrima2ole [23593-75-1] (8) the antiinflammatory agent ibuprofen [15687-27-1] (9) and the histamine H2-receptor antagonists famotidine [76824-35-6] (10) and cimetidine [51481-61-9] (11). 

Antacids are neutralizing agents. Examples are magnesium hydroxide, magnesium trisylicate and aluminium hydroxide. Prior to the introduction of histamine-H2 receptor antagonists and proton pump inhibitors, they were the standard drugs for the treatment of duodenal/ peptic ulcers. Today their clinical use is limited to the treatment of dyspepsia and the symptomatic relieve for patients with peptic ulcers. 

The following amides prepared from 4-(3-nitro-l-pyrazolyl)butanoic acid, CDI, and primary amines represent partial structures of the histamine H2-receptor antagonists roxatidine, cimetidine, ranitidine, and famotidine [37]... 

Azolides used as inhibitors for monoamine oxidase1171 or human leucocyte elastase,1181 as inductors of recessive lethal genes in Drosophila,1191 as histamine H2-receptor antagonists,1201 as anti-ulcer agents,1211 or as pharmacophores for anthelmintic, analgesic, and antimicrobial activity 1221... 

Black, J. W., Leff, R, and Shankley, N. R, Further analysis of anomalous pXj values for histamine H2-receptor antagonists on the mouse isolated stomach assay, Br. J. Pharmacol., 86, 581-587, 1985. 

Oxoquinolizine-3-carboxylates (e.g., 466) are excellent fluorophores that show a strong fluorescent response to Mg2+ but not to Ca2+, avoiding the very frequent interference between both cations <2001BCC203>. The fluorescence of indolo[2,3-tf]quinolizines has also been used for the design of fluorescent histamine H2 receptor antagonists as probes of this receptor <2003BML1717>. 

The bioslurry treatment successfully removed several of the PhC to non-detectable levels after 26 days three histamine H2-receptor antagonists (ranitidine, famotidine, cimetidine), two (1-blockers (atenolol, sotalol), one barbiturate (butalbital) and one antidiabetic compound (glibenclamide). The elimination of the sulfonamide antibiotics sulfapyridine (100%), sulfamethazine (91.0%) and... 

Nakamura, H., Sano, H., Yamazaki, M., Sugiyama Y., Carrier-mediated active transport of histamine H2 receptor antagonists, cimetidine and nizatidine, into isolated rat hepato-cytes contribution of type I system,... 

Cimetidine increases cyclic adenosine monophosphate concentration in smooth muscle, causes muscle to relax Antiulcerant Histamine H2 receptor antagonist, reduces volume of gastric... 

Wood, C. J. Simkins, M. A. Int. Svmp. on Histamine H2-Receptor Antagonists. 1973, Smith Kline and French Lab. Ltd., Welwyn, Garden City. 

Drugs that may affect fosamprenavir include antacids, carbamazepine, delavirdine, dexamethasone, histamine H2-receptor antagonists, HMG-CoA reductase inhibitors,... 

In the intense search for inhibitors of gastric acid secretion a new class of potent histamine H2-receptor antagonist was discovered. These 1,2,5-thiadiazole-l-oxides (27) were prepared by nucleophilic addition of primary amines to 3,4-dialkoxy-l,2,5-thiadiazole 1-oxide (25). Sequential addition of two different amines to positions C(3) and C(4), respectively, could be achieved via the 3-alkoxy-4-amino adduct (26) (Scheme 5) <82JMC207,82JMC210>. 

Changes in gastrointestinal pH Antacids, histamine H2-receptor antagonists and proton pump inhibitors reduce the absorption of... 

Lazzaroni M, Bianchi Porro G. Treatment of peptic ulcer in the elderly. Proton pump inhibitors and histamine H2 receptor antagonists. Drugs Aging 1996 9(4) 251-61. 

Histamine H2-receptor antagonists are well absorbed orally, although concurrent antacid therapy may reduce bioavailability by up to 30%. They are widely distributed in the body, crossing the blood-brain barrier and the placenta. Cimetidine, ranitidine and famotidine are extensively metabolised in the liver, and about one-third excreted unchanged in urine, while only one-third of nizatidine is metabolised (Table 11.1). Elimination half-life is increased up to tenfold in renal failure, and doses must be adjusted. 

Histamine H2-receptor antagonists are the mainstay of prevention of Mendelson s syndrome at present. Probably the best protection is afforded by a combination of H2-receptor blockade by ranitidine and a single oral dose of sodium citrate or bicarbonate. Because of its longer duration of action, and relative lack of enzyme inhibition, ranitidine is preferred to cimetidine for this purpose, although there is a latent period of 1-2 hours before it takes effect. Famotidine and nizatidine are probably equally effective in blocking acid secretion. 

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