ABSTRACT
Results of a preclinical study of the anxiolytic activity and safety of original Racium phytomedicine are presented. The preparation possessed high anxiolytic activity, exhibits a wide range of therapeutic effects, produces no lethality in male and female rats and mice upon single intragastric and intraperitoneal introduction in doses up to 5 g/kg (VI class of toxicity according to OECD), induces no pathologic effects upon prolonged (120 days) administration in these rodents, and has no local irritant and/or allergen action.
Subject(s)
Anti-Anxiety Agents/therapeutic use , Anxiety/drug therapy , Melissa/chemistry , Mentha piperita/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Valerian/chemistry , Animals , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/chemistry , Anxiety/physiopathology , Anxiety/psychology , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug-Related Side Effects and Adverse Reactions , Female , Injections, Intraperitoneal , Intubation, Gastrointestinal , Lethal Dose 50 , Male , Mice , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Rats , Sesquiterpenes/analysisABSTRACT
The radioprotective properties of 12 compounds of 9a-homo-13-thiaprostanoid series were investigated under gamma irradiation using the molecular model of beta-carotene radio-oxidation in oleic acid in vitro, erythrocyte radiomimetic model in ex vivo-in vitro system as well as in vivo radiation damage in mice. Most of these compounds stimulated the radio-oxidation of beta-carotene, however in this model two prostanoids with natural alpha-chain displayed radioprotective properties. Expressed membrane stabilizing effect of two 9a-homo-13-thiaprostanoid nor-analogues was revealed in radiomimetic model experiments. Two 10, 10-dimethyl-13-thiaprostanoids raised animal radioresistance during in vivo experiments.
Subject(s)
Prostaglandins/therapeutic use , Radiation Injuries, Experimental/drug therapy , Radiation-Protective Agents/therapeutic use , Animals , Carotenoids/radiation effects , Drug Evaluation, Preclinical , Erythrocytes/radiation effects , Female , Male , Mice , Radiation Injuries, Experimental/mortality , Rats , Structure-Activity Relationship , beta CaroteneSubject(s)
Anti-Inflammatory Agents/pharmacology , Azasteroids/pharmacology , Hormones/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Azasteroids/chemistry , Blood Glucose/drug effects , Blood Glucose/metabolism , Body Temperature Regulation/drug effects , Cell Division/drug effects , Female , Histamine Antagonists/pharmacology , Hormones/chemistry , Liver Glycogen/metabolism , Male , Mice , Pain Threshold/drug effects , Rats , Rats, Wistar , RectumABSTRACT
The pharmacokinetic investigation and the study of metabolism of an immunostimulator of 8-azasteroid series were performed on a single-compartment model. The main pharmacokinetic parameters of the immunomodulator in mice were established using different routes of administration. The maximal accumulation of tritium-labeled 8-azasteroid was recorded in the kidneys, liver and lung. The character of distribution changes with time. The half-life period is in the range of from 0.69 to 1.4 hours at different routes of administration. The total clearance is 0.49 ml/min, the area under the pharmacokinetic curve--3.8-8.1 micrograms/h/ml. On the model of the monooxygenase cytochrome P-450-containing system of the liver microsomes there was confirmed the formation of two metabolites preliminarily isolated from the mouse urine. By the character of resorption, distribution, elimination this 8-azasteroid immunoactivator is close to the agents of glucocorticoid series.
