Histamine receptors classification

Hill SI, Ganellin CR, Timmerman H et al (1997) International Union of Pharmacology XIII Classification of histamine receptors. Pharmacol Rev 49 253—278... 

It was noted, however, that a subset of responses known to be triggered by histamine failed to be blocked by the classical antihistaminic drugs. This, as well as further sophisticated pharmacological work, led to the classification of histamine receptors as and Hg. To simplify grossly, the receptor controls the responses familiar to every hayfever sufferer these effects can be alleviated readily by classicial antihistamines. The latter interestingly bear little or no structural similarity to histamine... 

Hill, S. J., Ganellin, C. R., Timmerman, H. etal. International Union of Pharmacology. XIII. Classification of histamine receptors. Pharmacol. Rev. 49 253-278,1997. 

Chand N, Eyre P Classification and biological distribution of histamine receptor subtypes. Agents Actions 1975 5 277-295. 

Hj histamine receptor blockers can be grouped according to their chemical structures ethanolamine derivatives (diphenhydramine, clemastine) ethylenediamine derivatives (tripe-lennamine, pyrilamine) alkylamines (chloropheniramine, dexchlorpheniramine, brompheniramine) piperazines (cycUzine, meclizine, hydroxizine) phenothiazines (promethazine, trimeprazine) piperidines (cyproheptadine, diphenylpyraline) and others that do not belong to a specific chemical classification (terfenadine, astemizole). 

The early antihistamines. Hi histamine receptor antagonists, bore some structural resemblance to histamine and, like histamine, contained an ethylamine group. However, the structures of the many antihistamines that are available are disparate, and the traditional classification according to chemical structure (ethanolamine, ethy-lenediamine, alkylamine, piperazine, and phenothiazine) is outdated, since the second-generation antihistamines, such as terfenadine and astemizole, do not readily fit into the old classification system (2). 

Histamine receptors were reviewed in 1973 before the advent of the H2 antagonists later developments are described in reference 4, and the subject was mentioned briefly in these reports in 1975 and 1977. The classification and distribution of histamine receptors has been discussed by Black and reviewed by Chand and Eyre. The Physiological Society of Philadelphia held a symposium on histamine receptors in 1977, the proceedings of which are in press. A symposium was held in 1978 at the Vlth International Conference on Medicinal Chemistry, Brighton, England (proceedings to be published). In addition, there have been several symposia on H2-receptor histamine antagonists, mainly concerned with clinical aspects. 

Histamine receptors have been classified into two major subtypes, H, and H2, on the basis of quantitative studies on isolated peripheral tissues. Histamine H,-receptors mediate the contractile actions of histamine on numerous visceral smooth muscles, most notably from the trachea, ileum and uterus of the guinea-pig [36-39]. These responses are antagonized by the classical -antihistamines [36-39] such as mepyramine (1) [36] and diphenhydramine (3) [40] (see Figure 2.1). Histamine also stimulates the secretion of acid by stomach, increases the rate of contraction of guinea-pig isolated atria and inhibits electrically evoked contractions of rat isolated uterine horn [41 ]. However, these responses are not affected by H, -receptor antagonists and have been defined as histamine H2-receptor responses following the development of specific antagonists to these responses such as burimamide [41], cimetidine [42] and ranitidine [43]. The distribution and classification of histamine H,-and H2-receptors in various mammalian peripheral tissues have been reviewed elsewhere [44-46a]. 

This classification is a bit more specific than the first, since it is identifying a system with which the drugs interact. It is, however, still a system with several stages and so the same point can be made as before—for example, one would not expect all antihistamines to be similar compounds since the system by which histamine is synthesized, released, interacts with its receptor, and is finally removed, can be attacked at all these stages. 

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