GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3receptor antagonists. The functional activity of these ligands on the histamine H3receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-α-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2values of 7.9±0.1 and 8.5±0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3receptors. Copyright (C) 1998 Elsevier Science B.V. All rights reserved.
Tedford, C. E., Hoffmann, M., Seyedi, N., Maruyama, R., Levi, R., Yates, S. L., … Phillips, J. G. (1998). High antagonist potency of GT-2227 and GT-2331, new histamine H3receptor antagonists, in two functional models. European Journal of Pharmacology, 351(3), 307–311. https://doi.org/10.1016/S0014-2999(98)00396-3