Histamine 2HCl

Histamine is an organic nitrogen compound, acts on target cells in mammalian brain via stimulation of Histamine 1/2.

[New target for the inhibitors of gastric acid secretion. Inhibition of myosin and actin activities via the apical membrane of parietal cells in dogs].[Pubmed:14727528]

Nihon Yakurigaku Zasshi. 2003 Nov;122 Suppl:74P-77P.

This report aims to highlight drugs that are able to inhibit parietal cells from the luminal side, resulting in suppressed gastric acid secretion. Histamine 2HCl was i.v. given continuously to obtain a submaximal stimulation of gastric acid secretion. Wortmannin and ME 3407 (a myosin light chain kinase inhibitor) and cytocharasin D (actin polymerizing inhibitor) were locally applied to denervated gastric pouches prepared in dogs for 5 to 30 min. Each drug, administered 0.5 hr before or 1 hr after histamine infusion was commenced, significantly inhibited stimulated-gastric acid secretion in a time-dependent manner. The antisecretory effect persisted for more than 24 hrs in the case of Wortmannin and 9 hr in the case of ME 3407 at a dosage 1 and 3 mg/pouch for 30 min, respectively. ME 2407, however, had no antisecretory effect when i.v. administered after histamine infusion, or orally administered before histamine infusion. Such results strongly suggest that the apical membrane of parietal cells possesses a ME 4307, Wortmannin and cytocharasin D sensitive portion similar to the basolateral membrane that usually mediates gastric acid secretion. The apical membrane represents an intriguing target for developing new antisecretory drugs, as well as for elucidating the functional features of parietal cells.

[Effects of ranitidine, a new histamine H2-receptor antagonist, on histamine- and aspirin-induced gastric ulcers in rats and dogs (author's transl)].[Pubmed:6120886]

Nihon Yakurigaku Zasshi. 1981 Dec;78(6):549-55.

Male donryu rats (200-220 g) and mongrel dogs of both sexes (7-20 kg) were used. Histamine-induced ulcers: Histamine 2HCl (100 mg/kg) was given i.p. to 24 hr-fasted rats and the animals were killed 4 hr later. Histamine 2HCl in beeswax (20 mg/kg) was given i.m. to dogs once daily for 5 days and the animals were killed on the 6th day. Aspirin-induced ulcers: Aspirin (100 mg/kg) was given p.o. to the 24 hr-fasted rats and dogs twice (15 h apart) and the animals were killed 9 hr after the second administration of aspirin. Either the length (mm) or ares (mm2) of each ulcer was measured, summed, and used as an ulcer index. Cimetidine and gefarnate were used as reference drugs. Ranitidine dose-dependently inhibited both histamine- and aspirin-induced ulcers in rats and dogs. On the basis of ED50, the antiulcer effect of ranitidine on histamine-induced ulcers was about two times (in rats) or 9 times (in dogs) more potent than cimetidine. However, the antiulcer effect of ranitidine on aspirin-induced ulcers was 1.7 times more potent than cimetidine (in rats) or almost equal (in dogs) to cimetidine. Gefarnate had an insignificant effect on both histamine- and aspirin-induced ulcers.

The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines.[Pubmed:18172439]

Nat Rev Drug Discov. 2008 Jan;7(1):41-53.

Histamine has a key role in allergic inflammatory conditions. The inflammatory responses resulting from the liberation of histamine have long been thought to be mediated by the histamine H1 receptor, and H1-receptor antagonists--commonly known as antihistamines--have been used to treat allergies for many years. However, the importance of histamine in the pathology of conditions such as asthma and chronic pruritus may have been underestimated. Here, we review accumulating evidence suggesting that histamine indeed has roles in inflammation and immune function modulation in such diseases. In particular, the discovery of a fourth histamine receptor (H4) and its expression on numerous immune and inflammatory cells has prompted a re-evaluation of the actions of histamine, suggesting a new potential for H4-receptor antagonists and a possible synergy between H1 and H4-receptor antagonists in targeting various inflammatory conditions.

Histamine and histamine intolerance.[Pubmed:17490952]

Am J Clin Nutr. 2007 May;85(5):1185-96.

Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.