Farmakologiia i toksikologiia最新文献

There were found significant differences in the pharmacokinetics of a new psychotropic drug with nootropic action ONC-10 following a long-term administration to the offspring of the intact animals as compared with the pharmacokinetics after a single administration: an increase of the drug content in plasma with a simultaneous decrease of clearance and the volume of distribution. A long-term administration of ONC-10 to the offspring of the alcoholized animals led to a decrease of the plasma drug level that was related to not only an increase of the constant of elimination and clearance of the drug but also an enhancement of the processes of its biotransformation and the appearance of the main metabolite.

Three and ten days after the administration of CCl4 (subcutaneously, once, 4 ml/kg of 50% oil solution) there were found a decrease of the rate of antipyrine elimination (intravenously, 50 mg/kg) from the blood plasma, an increase of the total bilirubin content, ALT activity and stimulation of lipid peroxidation processes. Cordiamine administration (subcutaneously, twice a day, 3 and 10 days) exerts the normalizing effect.

The effect of adamanthylamides of 1,3-diphenylptrazol-4-carbonic acids on the system of the liver microsomal monoxygenases was studied. A potent induction of the liver cytochrome P-450 by 1,3-diphenylpyrazol-5-methyl-4-carbonic acid, N-methyl-N-(adamant-1-il)amide was found. As a consequence of the induction of the liver cytochrome P-450, the compound reduced by 40% the degree of the delayed type hypersensitivity in mice.

The pro- and anti-inflammatory activity of new structural analogues of the platelet-activating factor (PAF) was studied. It was found that three PAF analogues inhibit PAF-induced rat paw edema in a dose-dependent manner. The anti-inflammatory activity of one of the PAF analogues upon PAF- or carrageenan-induced inflammation was comparable or in some extent exceeded that of dexamethasone.

The morphofunctional state of different links of the sympathoadrenal system under the action of neuroleptics haloperidol and sulpiride was studied on the model of immobilization stress in rats. The drugs were shown to possess the effect of the pharmacological correction of hormone content in the adrenals and the level of the neuromediator activity of the adrenergic nerves at different stages of immobilization stress. The data obtained indicate the anti-stress action of the studied neuroleptics. The effect of sulpiride is noted both in the early (the stage of anxiety) and late (the stage of exhaustion) periods of immobilization. The action of haloperidol is mainly limited to the stage of anxiety.

The effect of a high-affinity C1A serotonin receptor agonist flesinoxan on the arterial blood pressure and the heart rate in normotensive Wistar rats, spontaneously hypertensive rats and inherited stress-induced arterial hypertension rats was studied. It was shown that both peripheral and central administration of flesinoxan produces a decrease of blood pressure and heart rate. However, a reduction of heart rate was more pronounced at the drug peripheral administration. The sensitivity to flesinoxan in the hypertensive rats was greater than in the normotensive rats.

In experiments of albino rats neurotropin injection was shown to increase the latency of the tail-flick test in response to the nociceptive thermal stimulus and didn't change the threshold of the test in response to the nociceptive electroskin stimulus. The administration of the antiserum to beta-endorphin lowered the threshold and the latency of the tail-flick test in response to both stimuli. The preliminary administration of neurotropin reduced the hyperalgesic effect of the antiserum on both nociceptive stimuli.

Neurotropin was developed by Nippon Zoki Pharmaceutical Co. Ltd. It is produced by inoculating vaccine virus into rabbits and the effective substances are extracted from neuro-immuno inflamed cutaneous tissue. In the present study it was found that intraperitoneally administered neurotropin potently inhibits naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Also we get the experimental evidence that neurotropin increases morphine action but has no positive-reinforcing properties. These data indicate the possibility of testing neurotropin as a medicine for treating opiate-abused patients.

The processes of elimination and distribution of the synthetic steroidal drugs prednisolone and dexamethasone in the internal organs of Wistar rats were studied by the method of radioisotopes and high performance liquid chromatography. It was shown that the main route of excretion is the elimination with the urine. Prednisolone does not undergo conjugation and dexamethasone is glucuronidated by approximately 20%. The conclusion is made about the dependence of the main pharmacokinetic parameters on the concrete route of metabolism of each drug.