V. P. Zherdev

Regional and Subcellular Localization of Cycloprolylglycine in Rat Brain

HPLC analysis showed that endogenous cyclopeptide cycloprolylglycine exhibiting mnemotropic and anxiolytic properties is nonuniformly distributed between brain structures in rats: its contents in the whole brain, cortex, and hippocampus were 29.2±1.6, 38.9±8.0, 126.4±32.4 nmol/g, respectively. Cycloprolylglycine distribution between subcellular fractions of brain neurons is also nonuniform: 60% cyclopeptide appeared in the nuclear fraction.

Tissue availability of afobazole and its major metabolites in rats.

Intraperitoneally injected afobazole and its major metabolites are intensively distributed in highly vascularized tissues of rats, including the liver, spleen, and kidneys; the content of these compounds in moderately and poorly vascularized tissues (muscles and mesentery) is much lower. Afobazole and its metabolites possess intermediate ability to penetrate into the brain.

Assay of caffeine and its metabolites in the rat blood plasma using HPLC as a method for determination of metabolic ratios

A technique has been developed for the assay of caffeine and its metabolites in biological liquids (the rat blood plasma). The analysis was carried out using high-performance liquid chromatography with an ultraviolet detector. The limits of quantification (LOQ) for caffeine, paraxanthine, theobromine, and theophylline were calculated to be 10 ng/mL, and the LOQ of 1,3,7-trimethyluric acid was 25 ng/mL.

Excretion of afobazole and its metabolites with urine and feces in rats.

The amount of afobazole and identified metabolites was measured in the urine and feces of rats after intraperitoneal and peroral administration of the drug in a dose of 25 mg/kg. Over 1 day after intraperitoneal or peroral treatment with afobazole, urine and feces contained 0.1% initial compound (from administered dose) and 42.1% metabolites.

Relationship between physicochemical characteristics and pharmacokinetic parameters of 1,4-benzodiazepine derivatives

A rational targeted search for new effective drugs of the benzodiazepine group should be based on established relationships between the physicochemical properties of compounds and their pharmacological activity, the direction and rate of biotransformation, and the pharmacokinetic parameters [1]. Correlations between these factors make possible drawing reliable judgments about the rate of absorption from the gastrointestinal tract, the time of attaining maximum concentration in the blood, the time of circulation in the organism, and the rates of accumulation and elimination of new drugs, based on the results of analysis of the known data for analogous substances. This aim of this study was to determine some important physicochemical characteristics (dissolution rate constant, diffusion rate constant, lipophilicity constant) of a series of 1,4-benzodiazepine derivatives and to establish relationships between these values and the parameters of pharmacokinetics of these compounds in rats.

Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration

Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.

Excretion of Compound M-11 and Its Metabolites with Urine and Feces in Rats

The excretion of compound M-11 and its metabolites with the urine and feces was studied in rats after intraperitoneal and oral administration in a dose of 25 mg/kg. Experiments showed that 1% metabolites were detected in excretions over 24 h irrespective of the route of administration, while the initial compound was not found even in trace amounts.

Determination of oxidation phenotype in inbred C57Bl/6 and BALB/C mice

Antipyrine oxidation was studied in C57BL/6 and BALB/c inbred mice. It was found that C57BL/6 are weak oxidant but BALB/c are strong oxidants of antipyrine. Animals F1 hybrids inherited the high capacity of antipyrine oxidation.

Metabolism of a Novel Anxiolytic GML-1 in Rats

Metabolism of a novel anxiolytic GML-1 (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pirazin-3-carboxamide) in rat blood plasma was studied by HPLC-mass spectrometry. Three biotransformation products with the corresponding molecular ions were detected. A conclusion was made that the main pathways of GML-1 metabolism are oxidative reactions yielding hydroxylated, methylated, and demethylated metabolites.

Development and Validation of the Quantification of GML-1 Compound (N-benzyl-N-methyl-1-phenylpyrrolo[1,2-A] pyrazine- 3-carbamide) in the Blood Plasma of Rats by HPLC–MS

The technique of quantitative determination of a new compound, possessing anxiolytic activity, GML-1 in the blood plasma of rats is developed and validated. The analysis is performed by HPLC–MS. The method is linear in the range of 50–1000 ng/mL. 83.63% of GML-1 was recovered. The detection limit was 25 ng/mL.