Histamine selective agonists

Activation of histamine receptors with histamine and selective agonists such as dimaprit (205) and impromidine (206) results ia gastric acid... 

In contrast to the development of selective agonists for the H and H> receptor, potent agonists for the Hi receptor can be obtained by simple modification of the histamine molecule. Histamine itself is already a rather potent agonist of the Hv receptor, although it is of course not eery selective. 

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. 

I.J.P. de Esch, The synthesis of cyclopropylhistamine, a new rigid and selective Histamine H3-agonist. Submitted for publication. 

Histamine H2-receptors are of the seven-transmembrane G-protein-coupled superfamily, and couple positively to the adenylyl cyclase (GJ pathway. Selective agonists include amthamine, dimaprit and impromidine. They also have actions at the other histamine receptor types impromidine and dimaprit have Hs-antagonist properties, and amthamine is a weak agonist at the H3 receptor. Also, 4(5)-methylhistamine has been used experimentally. 

Histamine Receptor Agonists. Selective Hi receptor agonists decrease both NREM and REM sleep stages. This action can be prevented by pretreatment with Hi antagonists. In addition, it seems that blockade of CNS Hi receptors leads to sedation accounting for the well-known sedative activity of antihistamines (36). 

Kazuta, Y, Hirano, K., Natsume, K., Yamada, S., Kimura, R., Matsumoto, S.-i., Furuichi, K., Matsuda, A., Shuto, S. Cyclopropane-based conformational restriction of histamine. (lS,2S)-2-(2-Aminoethyl)-l-(l//-imidazol-4-yl)cyclopropane, a highly selective agonist for the histamine H3 receptor, having a cis-cyclopropane structure. J. Med. Chem. 2003, 46, 1980-1988. 

The aim of the present review is to examine the evidence for the presence of histamine receptors in the mammalian central nervous system and to review their properties. For the reasons outlined above, the scope of this review has been limited to recent in vitro biochemical studies where a quantitative comparison can be made between the properties of central and peripheral receptor systems. It is accepted, however, that the determination of the physiological r61e or r61es of histamine in mammalian brain will rely eventually on the availability and careful in vivo use of highly selective agonists and antagonists for the different classes of histamine receptor. 

The chemical structures of some selective H,- and H2-agonists are given in Figure 2.5 and the relative potencies of a range of histamine receptor agonists of H,-, H2- and the putative H3-receptor are given in Table2.3. 

Figure 2.10. Effect of histamine (9) and the H2-selective agonist impromidine (A) on cyclic AMP accumulation in slices of rabbit cerebral cortex. Values are expressed as a percentage of the maximum...

Support for an interaction between two components in the final cyclic AMP response to histamine in guinea-pig hippocampal and rabbit cerebral cortical slices has been provided with H,- and H2-selective agonists. In hippocampal slices the H2-selective agonists, impromidine and dimaprit, produced maximal cyclic AMP responses which were much less than the maximal response elicited by histamine [ 165, 195]. The extent of the stimulation appears to vary between experiments, ranging from 24% [165] to 62% [195] of the response to histamine. However, the extent of the cyclic AMP accumulation elicited by... 

In a similar way, o), co-diphenyl-alkyl chains ( butterflies ) were also attached to L-glutamic acid to yield Glu m3 glutamate metabotropic m3 receptor-selective agonists and to histamine, to yield the potent histamine Hj receptor agonists histaprodifen and methylhistaprodifen (Fig. 19.49). 

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