[Hepatoduodenal circulation and excretion of the new GABA derivative citrocard].

Pharmacokinetic investigation of a new gamma-aminobutyric acid (GABA) derivative cirtocard showed that, upon the intravenous introduction, the drug is determined in high concentrations in organs of elimination--the liver and kidneys. The tissue accessibility amounts to 1.341 for the liver and 4.053 for the kidneys and the separation factor is 1.041 for the liver and 4.486 for the kidneys. The study of drug excretion showed that cirtocard is determined in the urine for 48 h, its nephritic clearance being 0.047 L/h and extra-nephritic clearance, 0.33 L/h. For the unchanged substance, a large significance ofhepatoduodenal circulation is low probable, since no more than 1 - 2% of the introduced dose was isolated with bile over entire experiment. It is established that the removal of the unchanged substance does not exceed 10% of the introduced dose. There is high probability of hepatoduodenal circulation and excretion of the preparation in the form of metabolites.

[Absolute bioavailability of the adenine derivative VMA-99-82 possessing antiviral activity].

Investigation of the main pharmacokinetic parameters of adenine derivative VMA-99-82 in rats showed large values of the half-life (T1/2 = 11.03 h) and the mean retention time of drug molecules in the organism (MRT = 9.53 h). A high rate of the drug concentration decrease in the plasma determines a small value of the area under the pharmacokinetic curve (AUC = 74.96 mg h/ml). The total distribution volume (V(d) = 10.61 l/kg) is 15.8 times greater than the volume of extracellular fluid in the body of rat, which is indicative of a high ability of VMA-99-82 to be distributed and accumulated in the organs and tissues. The absolute bioavailability of VMA-99-82 is 66%.

[Effect of new derivatives of natural nitrogen-containing compounds on the level and metabolism of biogenic amines in brain structures and the life span of rats].

Effects of the analogs of transmitter amino acids on the level of biogenic amines and their metabolism in various structures of brain and on the life span of rats have been studied.

[Neurochemical mechanisms of antidepressant action of new adenine derivative].

We have studied the influence of the new adenine derivative VMA-99-82 on the exchange of monoamines and their metabolites in the brain of Wistar rats. In addition, the effect of VMA-99-82 on binding of 5-HT1A and 5-HT2A serotonin receptors and the system of 3H-serotonin reuptake in the brain synaptosomes has been studied in vitro. It is established that VMA-99-82 at a dose of 10 mg/kg has no affinity to 5-HT1A and 5-HT2A serotonin receptors and produces no effect on the reuptake of [3H]-5-HT. It is suggested that VMA-99-82 has a modulating effect on ion channel NMDA receptor complex of the glutamatergic system, which leads to the manifestation of antidepressant activity.