Novel histamine H3-receptor antagonists

Schlicker E, Kathmann M, Reidemeister S, Stark H, Schunack W (1994) Novel histamine H3 receptor antagonists affinities in an H3 receptor binding assay and potencies in two functional H3 receptor models. Br J Pharmacol 112 1043-1048 + 113 657 (erratum). 

Stark, H., Sadek, B., Krause, M., Huels, A., Ligneau, X., Ganellin, C. R., Arrang, J.-M., Schwartz, J.-C., Schunack, W. Novel Histamine H3-Receptor Antagonists with Carbonyl-Substituted 4-(3-(Phenoxy)propyl)-1H-imidazole Structures like Ciproxifan and Related Compounds. J. Med. Chem. 2000, 43, 3987-3994. 

A. Pharmacophore"based screening for novel histamine H3"receptor antagonists... 

Identification and optimization of a novel series of histamine H3 receptor antagonists... 

Histamine decarboxylase knockout mice are unable to produce histamine and these animals are unable to maintain wakefulness in a novel environment. Systemic or intraventricular administration of histamine or Hi receptor agonists induces wakefulness whereas systemic or intraventricular administration of Hi receptor antagonists induces sleep. Local administration of an H3 receptor agonist in the TMN induces sleep whereas local administration of an H3 receptor antagonist into the TMN induces wakefulness. 

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... 

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