Histamine H3 agonists

Monti, J. M., Jantos, H., Ponzoni, A Monti, D. (1996). Sleep and waking during acute histamine H3 agonist BP 2.94 or H3 antagonist carboperamide (MR 16155) administration in rats. Neuropsychopharmacology 15, 31-5. 

Djuric, D.M., Nesic, M.T., Andjelkovic, I.Z., 1996. Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+, K+-ATPase. Mediators Inflammation 5, 69-74. 

Ea-Kim, L., Javellaud, J., Oudart, N., 1992a. In vivo cardiovascular effects of histamine H3-agonist and H3-antagonist. Fundam. Clin. Pharmacol. 6, 206. 

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

N.-Y. Shih, Imidazolyl-Alkyl-Piperazine and -Diazepine Derivatives as Histamine H3 Agonists/Antagonists, PCT Int. Patent Appl. WO 93/12093 (1993). 

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. 

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... 

Lamberty, Y., Margineanu, D. G., Dassesse, D. 8r Klitgaard, H. (2003). H3 agonist immepip markedly reduces cortical histamine release, but only weakly promotes sleep in the rat. Pharmacol. Res. 48, 193-8. 

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. 

Drugs that act on the H3 receptor are being developed for the treatment of obesity, sleep disturbances, epilepsy and cognitive disorders. The ability of histamine to promote arousal, suppress appetite, elevate seizure threshold and stimulate cognitive processes implies that compounds able to enhance the release of neuronal histamine should mimic these effects. Several H3 antagonists currently in development demonstrate such activity and show promise as effective and novel therapeutic agents [40, 84-86]. Because H3 agonists suppress the release of... 

However, when the authors tried to predict six new compounds that acted on the histamine Hi or H3 receptors, they were all overestimated by the derived models. This tendency was especially noticeable for the model based on molar volume and van der Waals surface (Eq. 13). Incorporation of the new histamine Hi agonists into the models resulted in rather degraded statistics (Eq. 14-15) ... 

Azomethine prodrugs of (R)-a-methylhistamine (11.60) offer an apt illustration of this approach. (R)-a-Methylhistamine (11.61) is potent and selective as a histamine H3 receptor agonist, but its medicinal usefulness in hu-... 

M. Krause, A. Rouleau, H. Stark, P. Luger, R. Lipp, M. Garbarg, J. C. Schwartz, W. Schunack, Synthesis, X-Ray Crystallography, and Pharmacokinetics of Novel Azome-thine Prodrugs of (R)-a-Methylhistamine Highly Potent and Selective Histamine H3 Receptor Agonists , J. Med. Chem. 1995, 38, 4070 - 4079. 

Histamine H3 antagonists 5-HT3 receptor agonist 5-HTlA receptor agonist 5-HT6 antagonist Serotonin stimulant FK-960 Fujisawa... 

Lin J-S et al An inverse agonist of the histamine H3 receptor improves wakefulness in narcolepsy Studies in orexin-/- mice and patients. Neurobiol Dis 2008 30 74. [PMID 18295497]... 

Howson W, Parsons ME, Raval P, Swayne GTG (1992) Two novel, potent and selective histamine H3 receptor agonists. Bioorg Med Chem Lett 2 77-78. 

Van der Goot H, Schepers MJP, Sterk GJ, Timmerman H (1992) Isothiourea analogues of histamine as potent agonists or antagonists of the histamine H3-receptor. Eur J Med Chem 27 511-518. 

---