H,-receptor antagonists

Second-Generation Receptor Antagonists. Because of undesirable side effects caused by classical H receptor antagonists, dmgs... 

Hj Antihistamine Treatment in Allergic Diseases. H -receptor antagonists are used for the symptomatic treatment of several allergic... 

Atopic Dermatitis. The mechanism of itching associated with atopic dermatitis remains unknown, but histamine is almost certainly involved to some extent as histamine concentrations are increased in the skin and in the plasma of patients with this disorder (39,42). Second-generation H receptor antagonists, unlike first-generation H receptor antagonists, have not been uniformly found to be effective in relieving itching in atopic dermatitis, which may be related to the absence of a sedative effect (43). 

Antazoline H,-receptor antagonist Available only in combination with naphazoline... 

Levocabastine H,-receptor antagonist Downregulates intracellular adhesion molecules, decreasing the inflammatory response may be used for up to 2 weeks... 

Emedastine H,-receptor antagonist inhibits eosinophil chemotaxis Superior Hrreceptor binding ability... 

Bakker, R. A., Wieland, K., Timmerman, H. and Leurs, R. Constitutive activity of the histamine H[ receptor reveals inverse agonism of histamine H receptor antagonists. Eur. J. Pharmacol. 387 R5-R7, 2000. 

Interestingly, penicillamine—a degradation product of penicillin and phenothiazines—the histamine H,—receptor antagonists, such as promethazine teoclate, methadilazine hydrochloride, trimeprazine tartrate are found to increase the cholesterol levels. 

Geriatric Considerations - Summary Azelastine is a potent H, receptor antagonist with minimal anticholinergic effects, it is used primarily as a nasal spray or ophthalmic solution but is well absorbed and can produce systemic effects such as headache and somnolence. 

HagermarkO, Levander S, Stable M A comparison of antihistaminicand sedative effects of some H,-receptor antagonists. Acta Derm Venereol i985,i i4 i 55-i 56. 

Most of the antihistaminics (H -receptor antagonists) have similar pharmacological actions and conventionally can be discussed together. 

The second generation H -receptor antagonist cetirizine is a reacemate consisting of equal quantities of 2 enantiomers, levocetirizine [(R)-enantiomer] and dextrocetirizine [(S)-enantiomer]. In vitro and human pharmacodynamic studies have provided evidence that levocetirizine is the more active enantiomer, accounting for most or all clinical antihistaminic activity of racemic cetirizine this activity of levocetirizine is seen at half the dose of cetirizine. 

As discussed earlier, receptors are responsible for histamine induced gastric acid secretion. H -receptors antagonists such as cimetidine, ranitidine, famotidine etc. are used in the treatment of peptic ulcer and are discussed in chapter Antiulcer agents. ... 

The first-generation H receptor antagonists have many actions in addition to blockade of the actions of histamine. The large number of these actions probably results from the similarity of the general structure (Figure 16-1) to the structure of drugs that have effects at muscarinic cholinoceptor, a adrenoceptor, serotonin, and local anesthetic receptor sites. Some of these actions are of therapeutic value and some are undesirable. 

When reboxetine was substituted for doxepin the cholesterol concentration returned to normal. Doxepin has particularly potent H receptor antagonist properties, which suggests that blockade of Hi receptors may play a role in the cholesterol raising properties of some psychotropic drugs. 

Ketotifen is a nonspecific, oral, mast cell stabilizer introduced in 1972 (1). The prominent biochemical-pharmacological activities of ketotifen are H,-receptor antagonism, phosphodiesterase inhibition, inhibition of the formation SRS-A, and inhibition of calcium flux in smooth muscle preparations all these actions are suited to prevent a development of asthmatic conditions. Promising results were obtained in early clinical trials ketotifen was equipotent with disodium cromoglycate in prevention of asthma induced by spontaneous excer-cise or by antigens. Also, ketotifen is more specific than clemastine as a H-,-receptor antagonist. However, more recent, controled trials failed to substantiate the early therapeutic optimism. The beneficial effect of ketotifen in the treatment of asthma is only small it was noted that this effect is associated with pronounced sedation (2). 

An interesting observation in our structure-activity studies was that ethylamine, a part of the histamine molecule, 4-(2-ethylamine)imidazole, known for a long time to be a potent stimulator of gastric secretion, also produced duodenal ulcers in rats (20,22). Furthermore, structural similarities also exist between dopamine and histamine H receptor antagonists metiamide and cimetidine (23,24). 

Zhang MQ, Leurs R, Timmerman H. Histamine H receptor antagonists. In Burger s Medicinal Chemistry and Drug Discovery. Wolff M E (Ed.).)ohn Wiley Sons, 1997. 

Buclizirte hydrochloride is (RS)-l-(4-ferf-butylbenzyl)-4-(4-chlorober zhy-dryl)piperazir e dihydrochloride. It contains not less than 99% and not more than 100.5% of C28H33C1N2-2HC1, calculated with reference to the dried substance. It is a histamine H-receptor antagonist and antiemetic. 

By blocking histamine binding to its site of action (receptors), e.g. using competitive H - and H -receptor antagonists. 

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