[Substituted 2,3,4,5-tetrahydro-1H-gamma-carbolines: new antagonists of histamine H1 receptors].


The properties of 2,3,4,5-tetrahydro-1H-gamma-carbolines containing acid, ether, and amido-substituents, were assessed as potential antagonists of histamine H1 receptors (H1R), capable of blocking histamine-induced calcium fluxes in SK-N-SH cells. The structure--activity relationship for their antagonistic activity is discussed. Among the gamma-carbolines used in the study, the antihistamine activity considerably depends on the nature of substituents in positions 2, 5, and 8 of the heterocycle. The most active antagonist, ethyl 3-(2-methyl-8-fluoro-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate, with high affinity to the H1R (Ki = 6.5 nM), produces no adverse effects on motor activity of mice in doses 1-40 mg/kg, which shows the absence of a sedative effect.

Cite this paper

@article{Ivashchenko2010Substituted2N, title={[Substituted 2,3,4,5-tetrahydro-1H-gamma-carbolines: new antagonists of histamine H1 receptors].}, author={Alexander V. Ivashchenko and O D Mit'kin and I. M. Okun' and Ramiz M. Salimov and Iu A Fedotov}, journal={Eksperimental'naia i klinicheskaia farmakologiia}, year={2010}, volume={73 11}, pages={25-9} }