ABSTRACT
The toxicity of new gamma-carboline derivative [ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carbolin-5-yl)-propionate dihydrochloride, CD-008-040] has been studied.
Subject(s)
Anti-Allergic Agents/adverse effects , Anti-Allergic Agents/pharmacology , Carbolines/adverse effects , Carbolines/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Humans , Male , MiceABSTRACT
The influence of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate dihydrochloride belonging to the class of gamma-carbolines on the allergic reactions (inflammation and systemic anaphylaxis) has been studied on laboratory animals. It was established that the given substance administered in a dose of 5 - 20 mg/kg exhibits a pronounced antiallergic action. Unlike many other antihistamine drugs, this gamma-carboline derivative probably does not produce sedative effect.
Subject(s)
Anti-Allergic Agents/therapeutic use , Carbolines/therapeutic use , Histamine Antagonists/therapeutic use , Anaphylaxis/drug therapy , Anaphylaxis/immunology , Animals , Guinea Pigs , Inflammation/drug therapy , Inflammation/immunology , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBAABSTRACT
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.
Subject(s)
Calcium/metabolism , Carbolines/pharmacology , Histamine H1 Antagonists/pharmacology , Motor Activity/drug effects , Receptors, Histamine H1/metabolism , Animals , Carbolines/chemistry , Cell Line , Drug Evaluation, Preclinical , Histamine H1 Antagonists/chemistry , Male , Mice , Structure-Activity RelationshipABSTRACT
The paper outlines materials on how to improve a method for indication of water viral pollution in different water objects of the environment, by applying a MFM filtration module based on tangentially radial-mode water microfiltration and viral concentration on the positively charged membranes, by using the secondary stage of concentration. Experimental and full-scale studies have demonstrated that this method for virus isolation has a high effectiveness and is based on the employment of the materials made in Russia. This determines its rapid introduction into the system for the sanitary-virological monitoring of practical laboratories of various departments, which will favor the higher efficiency of epidemiological surveillance as an integral part of nonspecific prophylactic measures of virus infections of water etiology.
