Histamine H2 receptor

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). 

Very recently, a very bold chemical model for histamine H2-receptors has been proposed using [18]aneN6-3H+ 84), which can chemically recognize histamine, histamine H2-agonists, and histamine H2-antagonists such as cimetidine XII or ranitidine XIII that are currently in world-wide use for treatment of peptic ulcers 85). 

In this histamine H2-receptor model, both histamine and its antagonists bind to [18]aneN6 3 H + forming 1 1 complexes at neutral pH, and the histamine antagonists are more strongly bound to the receptor model (see Fig. 9). Although this picture... 

FIGURE 1.7 Key compounds synthesized to eliminate the efficacy (burgundy red) and enhance the affinity (green) of histamine for histamine H2 receptors to make cimetidine, one of the first histamine H2 antagonists of use in the treatment of peptic ulcers. Quotation from James Black [10]. 

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 histamine H2-receptor (359 amino acids) is best known for its effect on gastric acid secretion. Histamine H2-receptor activation, in conjunction with gastrin and acetylcholine from the vagus, potently stimulate acid secretion from parietal cells. High concentrations of histamine are also present in cardiac tissues and can stimulate positive chronotropic and inotropic effects via H2-receptor stimulation and activation of adenylyl... 

These drug inhibit die action of histamine at histamine H2 receptor cells of die stomach, which then reduces die secretion of gastric acid and reduces total pepsin output. The decrease in acid allows the ulcerated areas to heal. Examples of histamine H2 antagonists include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid Pulvules), ranitidine (Zantac). 

Black, JW, Duncan, WAM, Durant, CJ, Ganellin, CR and Parsons, ME (1972) Definition and antagonism of histamine H2 receptors. Nature 236 358-390. 

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. 

Gantz, I., Schaffer, M., DelValle, J. et al. (1991). Molecular cloning of a gene encoding the histamine H2 receptor. Proc. Natl. Acad. Sci. USA 88, 429-33. 

Monti, J. M., Orellana, C., Boussard, M., Jantos, H. Olivera, S. (1990). Sleep variables are unaltered by zolantidine in rats are histamine H2-receptors not involved in sleep regulation Brain Res. Bull. 25, 229-31. 

Traiffort, E., Pollard, H., Moreau, J. et al. (1992). Pharmacological characterization and autoradiographic localization of histamine H2 receptors in human brain identified with [125I]iodoaminopotentidine. J. Neurochem. 59, 290-9. 

Traiffort, E., Vizuete, M. L., Tardivel-Lacombe, J. et at (1995). The guinea pig histamine H2 receptor gene cloning, tissue expression and chromosomal localization of its human counterpart. Biochem. Biophys. Res. Commun. 211, 570-7. 

Vizuete, M. L Traiffort, E., Bouthenet, M. L. et at (1997). Detailed mapping of the histamine H2 receptor and its gene transcripts in guinea-pig brain. Neuroscience 80, 321-43. 

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,... 

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