Histamine receptors agonists and antagonists

Leurs, R, Blandina, P, Tedford, C and Timmerman, H (1998) Therapeutic potential of histamine H3 receptor agonists and antagonists. Trends Pharmacol. Sci. 19 177-183. 

G. J. Durant (1979). Chemical aspects of histamine Hj-receptor agonists and antagonists. In ... 

Table 1. Ki values of several H3 receptor agonists and antagonists. [3H]histamine displacement was done on bovine whole brain membrane preparations of total bovine brain (particulate) and digitonin treated material...

A qualitative model for histamine H3 receptor agonists and antagonists... 

Ganellin, G. R., Durant, G. J. Histamine H2-Receptor Agonists and Antagonists. In M. E. Wolff (Ed.), Burger s Medicinal Chemistry, (4th ed., Chapter 48). New York Wiley Sons, 1981. 

The actions of histamine are mediated through at least three distinct receptors defined pharmacologically by the actions of the respective agonists and antagonists. Reviews have been pubHshed (16,17). 

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). 

Hf and H Receptors. Histamine exerts its actions by binding to receptors on cell membranes. Two types of histamine receptors, the Hi and H2 receptors, are known specific agonists and antagonists exist for each of these receptors. Black et al. (55) differentiated H and H2 receptors with the compounds, 2-methylhistamine and 4 methylhistamine. 2-Methylhistamine is active on tissues with H receptors 4-methylhistamine is active on tissues with H2 receptors. Classical antihistaminic drugs were developed in the 1930 s these compounds block H but not H2 receptors. Among the clinically used H -blockers are derivatives of ethanolamine, ethylenediamine, alkylamine, piperazine and phenothiazine (32). These agents are valuable in the treatment of... 

In the mouse uterus H3 receptors seem to be absent, since both agonists and antagonists of this receptor failed to modify noradrenaline release evoked by 100 mM K+ or electrical stimulation (Montesino et al., 1995). It would seem that prejunctional histamine receptors which modulate noradrenergic transmission belong to the Hj subtype. 

Coruzzi, G., Gambarelli, E., Bertaccini, G., Timmerman, H., 1995. Cardiovascular effects of selective agonists and antagonists of histamine H3 receptors in the anaesthetized rat. Naunyn-Schmiedeberg s Arch. Pharmacol. 351, 569-575. 

Solubilisation had little effect on the Kd of [3H]histamine binding. Saturation binding to the solubilised receptor protein yielded a Kd of 6.1 nM and a Bm x of 92 fmol/mg of protein. The differences between the inhibitory potencies of H3 specific agonists and antagonists between the particulate and the solubilised protein were generally minor, (table 1). The rank order of inhibitor potencies confirms that the binding was to the H3 receptor. 

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