Ivashchenko A V, Mit'kin O D, Okun' I M, Salimov R M, Fedotov Iu A
Eksp Klin Farmakol. 2010 Nov;73(11):25-9.
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.
对含有酸、醚和酰胺取代基的2,3,4,5-四氢-1H-γ-咔啉的性质进行了评估，它们作为组胺H1受体（H1R）的潜在拮抗剂，能够阻断组胺诱导的SK-N-SH细胞中的钙通量。讨论了它们拮抗活性的构效关系。在该研究中使用的γ-咔啉中，抗组胺活性很大程度上取决于杂环2、5和8位取代基的性质。最具活性的拮抗剂3-(2-甲基-8-氟-2,3,4,5-四氢-1H-γ-咔啉-5-基)丙酸乙酯对H1R具有高亲和力（Ki = 6.5 nM），在1-40 mg/kg剂量下对小鼠的运动活性没有不良影响，这表明没有镇静作用。
