Histamine-2 receptor pharmacology

Betazole (683) has been used as a chemical control substance for pharmacological characterization of histamine receptors (B-80MI40406), and shows a relative selective activity towards the H2-receptor. Betazole hydrochloride is used to diagnose impairment of the acid-producing cells of the stomach. 

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... 

Leurs, R., Smit, M. J. and Timmerman, H. Molecular pharmacological aspects of histamine receptors. Pharmacol. Ther. 66 413-463,1995. 

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

There are two distinct types of histamine receptors, H-l and H-2, with distinct pharmacological properties. There are about 2.5 x 105 H-l receptors per neutrophil, and these have a single dissociation constant of around 50 nM. Occupancy of these H-l receptors increases chemokinesis occupancy of H-2 receptors increases both chemokinesis and intracellular cAMP levels, but decreases chemotaxis and degranulation. 

Leurs R, Smit MJ. Timmerman H Molecular and pharmacological aspects of histamine receptors. Pharmacol Ther 1995 66 413-463. 

There is a diversity of histamine receptors. The H2, H3 and H4 receptors are of interest in gastrointestinal pharmacology. Histamine H2 receptors are G protein-coupled receptors which act by increasing intracellular cAMP to stimulate gastric acid production, and blockade reduces acid secretion. 

Table 15.1 Pharmacological activity associated with individual histamine receptors...

Raible, D.G., Lenahan, T., Fayvilevich, Y., Kosinski, R., Schulman, E.S., 1994 Pharmacological characterization of a novel histamine receptor on human eosinophils. Am. J. Respir. Crit. Care Med. 149, 1506-1511. 

The synthesis of imidazoles and the evaluation of their pharmacological activities can therefore be considered to be the key to a better understanding of the histamine receptors. Further new developments such as combinatorial technologies and the uprise of molecular biology will certainly play an important role in the need for and the synthesis and evaluation of new substituted imidazoles in the coming years. 

H3 receptors are hetereogeneous for three reasons species differences in amino acid sequence and, hence, pharmacology (Zaragoza et al. 2004) receptor oligomerization (Bakker 2004) and the existence of, so far, six splice variants, H3A, H3B, H3C, H3D, H3E, and H3F (Bakker et al. 2006). The latter three variants, H3D, H3E, and H3F, are retained intracellularly and may control the cell surface expression of H3A, H3B, and H3C. Since most reports on histamine receptor modulation of transmitter release only refer to the H3 receptor, not to the splice variants, I do not differentiate between these in the following. 

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