Histamine H3-receptors

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Imamura M, Lander HM, Levi R Activation of histamine H3-receptors inhibits carrier-mediated norepinephrine release during protracted myocardial ischemia. Comparison with adenosine Aj-receptors and a2-adrenoceptors. Circ Res 1996 78 475. 

Silver RB, Mackins CJ, Smith NCE, Koritchneva IL, Lefkowitz K, Lovenberg TW> Levi R Coupling of histamine H3 receptors to neuronal Na+/H+ exchange a novel protective mechanism in myocardial ischemia, Proc Natl Acad Sci USA 2001 98 2855. Silver RB, Poonwasi KS, Seyedi N, Wilson SJ, Lovenberg TW, Levi R Decreased intracellular calcium mediates the histamine H3-receptor-induced attenuation of norepinephrine exocytosis from cardiac sympathetic nerve endings. Proc Natl Acad Sci USA 2002 99 501. 

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. 

Pollard, H, Moreau, J, Arrang, JM and Schwartz, JC (1993) A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas. Neuroscience 52 168-189. 

The biology of the histamine H3 receptor has been detailed in several recent reviews and will not be discussed in great detail here [1-4]. Rather, we intend to draw attention to the major new biological and medicinal chemistry insights that have emerged in the histamine H3 research community over the last couple of years. 

The key to an understanding of the biology of the histamine H3 receptor is the fact that it is an inhibitory auto- and heteroreceptor. Activation of the H3... 

Although most of the medicinal chemistry effort in the H3 receptor field has been focused on the development of antagonists, there is some interest in agonists as well. Histamine H3 receptor agonists decrease the release of histamine in the central and peripheral nervous system and lead to a weakened histaminergic tone. In the brain, their effects will therefore be comparable to those of Hi receptor antagonists, with sedation and induction of sleep as a prominent observation. Indeed, H3 agonists such as the imidazoles... 

Arrang, J. M., Garbarg, M., Lancelot, J. C. et al. (1987a). Highly potent and selective ligands for histamine H3-receptors. Nature 327, 117-23. 

Clapham, J. Kilpatrick, G. J. (1992). Histamine H3 receptors modulate the release of [3H]-acetylcholine from slices of rat entorhinal cortex evidence for the possible existence of H3 receptor subtypes. Br. ]. Pharmacol. 107,... 

Ligneau, X., Lin, J., Vanni-Mercier, G. et at (1998). Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist. J. Pharmacol. 

McLeod, R. L., Aslanian, R., del Prado, M. et at (1998). Sch 50971, an orally active histamine H3 receptor agonist, inhibits central neurogenic vascular inflammation and produces sedation in the guinea pig. J. Pharmacol. Exp. Ther. 287, 43-50. 

Schlicker, E., Betz, R. Gothert, M. (1988). Histamine H3 receptor-mediated... 

Toyota, H., Dugovic, C., Koehl, M. et al. (2002). Behavioral characterization of mice lacking histamine H3 receptors. Mol. Pharmacol 62, 389-97. 

Vanni-Mercier, G Gigout, S., Debilly, G. Lin, J. S. (2003). Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands an electrophysiological study in freely moving cats. Behav. Brain. Res. 

Munzar, R, Tanda, G., Justinova, Z., Goldberg, S.R. Histamine h3 receptor antagonists potentiate methamphetamine self-administration and methamphetamine-induced accumbal dopamine release. Neuropsychopharmacology. 29 705, 2004. 

De Esch IJP, Mills JEJ, Perkins TDJ, Romeo G, Hoffmann M, Wieland K, Leurs R, Menge WMPB, Nederkoorn PHJ, Dean PM, Timmerman H. Development of a pharmacophore model for histamine H3 receptor antagonists, using the newly developed molecular modeling program SLATE. J Med Chem 2001 44 1666-1674. 

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