[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.
A V
AV
Ivashchenko
O D
OD
Mit'kin
I M
IM
Okun'
R M
RM
Salimov
Iu A
IuA
Fedotov
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006634:Histamine H1 Antagonists / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002243:Carbolines; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D002118:Calcium