[The effect of ximedon on cholesterol metabolism and experimental atherosclerosis in rabbits]. / Vliianie ksimedona na metabolizm kholesterina i éksperimental'nyi ateroskleroz u krolikov.

The effects produced by the two pyrimidine derivatives pyridinol carbamate (parmidine) and xymedon on cholesterol metabolism and experimental atherosclerosis were comparatively studied in rabbits. The rabbits were fed either a chow containing cholesterol (200 mg/kg body weight) or the same diet also containing xymedon (30 mg/kg body weight) or pyridinol carbamate (30 mg/kg body weight). Total plasma cholesterol showed 5.5- and 4.7-fold increases in the rabbits receiving only cholesterol or cholesterol + pyridinol carbamate, respectively, as compared with that in the animals on a standard laboratory chow. In the rabbits given cholesterol+xymedon, cholesterol levels were 24% less than that in the animals taking cholesterol alone. In these animals, the aortic atherosclerotic damage index (ADI) was equal to 24.1%, which was 1.8-fold less than that in the cholesterol-fed rabbits. In the rabbits given cholesterol+pyridinol carbamate, ADI was decreased by 1.7 times, but it did not differ from that in the hypocholesterolemic rabbits. At the same time xymidone and pyridinol carbamate reduced the hepatic levels of total and esterified cholesterol. To elucidate the mechanism of action of xymedon, it was studied for effects on cholesterol metabolism in cultured rabbit hepatocytes and murine macrophage J774. Xymedon did not alter the esterification and other parameters of cholesterol metabolism in the cultured hepatocytes. It is suggested that the hypocholesterolemic effect was realized at the level of intestinal rather than hepatic cholesterol metabolic changes. The investigations made on the murine macrophage J744 showed that xymedone reduced cholesterol esterification in macrophages, evidently by inhibiting the activity of the enzyme acyl-CoA: cholesterol acyltransferase. The anti-atherosclerotic effect of xymedon seems to result from reductions in plasma cholesterol levels and cholesterol esterification in blood vascular cells.

[The effect of dimethyl-(imidazol-1-yl) methanesulfonic acid on experimental atherogenesis in rabbits]. / Vliianie dimetil-(imidazol-1-il) metansul'fonovoi kisloty na éksperimental'nyi aterogenez u krolikov.

The hypocholesterolemic and antiatherosclerotic activities of the new imidazole derivative dimethyl-(imidazole-1-yl) methanesulfonic acid (1273) were investigated in rabbits fed through a probe either cholesterol, 200 mg/kg body weight, suspended in sunflower seed oil or that supplemented by imidazole, 15 mg/kg body weight, or its derivative 1273, 30 mg/kg body weight. Total cholesterol showed an 8-fold increase in all rabbit groups as compared to that in the animals fed a routine laboratory chow. In the agent 1273-given animals, the aortic atherosclerotic lesion index (ALI) was 7.8%, which was 2.4 times lower that in hypercholesterolemic animals untreated with this agent or treated with imidazole. Concurrently with a decrease in the aortic ALI, the agent 1273 lowered the rabbit hepatic levels of free and esterified cholesterol. The experimental findings of cultured rabbit hepatocytes suggest that the agent 1273 reduces hepatic cholesterol levels by inhibiting the de novo cholesterol synthesis. In vitro studies on murine J774 macrophages have demonstrated that inhibition of cholesterol esterification in the vascular wall macrophages is one of the possible mechanisms responsible for the antiatherosclerotic activity of this derivative of imidazole.

[The comparative characteristics of the antiatherogenic effect of xymedon and parmidine]. / Sravnitel'naia kharakteristika antiaterogennogo éffekta ksimedona i parmidina.

We've studied xymedon (30 mg/kg, 12 m) and parmidin (pyridinolcarbamate 30 mg/kg, 12 m.) effects on the development of experimental cholesterol atherosclerosis on rabbits. It was demonstrated that after the use of xymedon aorta damage reduces twice. Xymedon also prevents accumulation of cholesterol and fatty degeneration of the liver. Antiatherogenic effect of xymedon resulted comparable with the effect of parmidin. As it was demonstrated in the present investigation and in the previous ones in contrast to parmidin, xymedon normalizes the lipoproteins balance owing to increase of HDL cholesterol. It also has regenerative activity on endotheliocytes and immunomodulator properties. That can be of great importance for the anti-atherosclerotic effects of the medicine.

[Effect of cimetidine on experimental atherogenesis in rabbits]. / Vliianie tsimetidina na éksperimental'nyi aterogenez u krolikov.

It was shown that cimetidine (10 mg/kg, 12 weeks) reduces the frequency and the degree of affection of rabbit's aortas during experimental cholesterol atherosclerosis. The protective effect of cimetidine on the liver where the contents of lipids, especially cholesterol esters reduced considerably, was noted. The nature of the fatty dystrophy changes from the large-drop to the small-drop one which should be considered as a favourable phenomenon. The anti-atherogenic and hepatoprotective effects of cimetidine can be explained by slowing-down of lipoperoxidation processes which is proved in respect of blood and aorta walls.

[An analysis of the cardiovascular reactions due to mebikar]. / Analiz serdechno-sosudistykh reaktsii, vyzvannykh mebikarom.

The effect of a tranquillizer mebicar on the cardiovascular system was studied experimentally. The drug was shown to increase the myocardial contractility, to exert a slight effect on the cardiac rhythm, to dilate the peripheral arteries. The analysis revealed that the vasodilating properties of mebicar are related to its central neurotropic action. The cardiac stimulating effects depend on the involvement of mebicar in the myocardial metabolism.

[Mechanisms of the antishock action of mebikar]. / Mekhanizmy protivoshokovogo deistviia mebikara.

The tranquilizer mebicar produces an antishock action, normalizes different links of mediator, acid-base and oxygen homeostasis. Mebicar decreases arterial pressure and the tone of peripheral vessels insignificantly and for a short period.

[Comparative evaluation of antishock activity of various Soviet pharmacological agents]. / Sravnitel'naia otsenka protivoshokovogo deistviia nekotorykh otechestvennykh farmakologicheskikh preparatov.

On the basis of experimental and clinical studies the authors recommend to use mebikar with promedol in complex with other drugs for the treatment of traumatic shock in the prehospital and hospital periods. It was found to substantially improve results of the antishock therapy.

[Comparative analysis of the behavioral, neurochemical and autonomotropic effects of mebikar and diazepam]. / Sravnitel'nyi analiz nekotorykh povedencheskikh, neirokhimicheskikh i vegetotropnykh éffektov mebikara i diazepama.

It has been shown that the tranquilizers, diazepam (a 1,4-benzodiazepine derivative) and mebicar (a derivative of bicyclic bisureas) produce one-line inhibition of the production of the conditioned reflex of active avoidance in rats and of their "open-field" motor activity. Both the drugs change the balance of neuroactive amino acids in the animals' brain. However they produce different changes: diazepam increases the content of asparaginic and glutamic acids, while mebicar raises that of gamma-butyric acid. No interrelationship was found between psychotropic and vegetotropic effects of the tranquilizers.

[Protective effect of the psychotropic preparations diazepam, sodium oxybutyrate and mebikar in experimental arrhythmias]. / O zashchitnom éffekte psikhotropnykh preparatov diazepama, natriia oksibutirata i mebikara pri éksperimental'nykh aritmiiakh.

It was shown that the psychotropic agents diazepam (1-2 mg/kg), sodium hydroxybutyrate (50-100 mg/kg) and mebicar (250-500 mg/kg) exert a protective action in experimental arrhythmias. This effect is determined by the ability of the drugs to reduce intoxication phenomena, as well as by their antihypoxic and stress-protective properties. On the other hand, the drugs exert an antiarrhythmic effect proper, interfering with potassium ion balance. The protective effects of diazepam, sodium hydroxybutyrate and mebicar enable their application in combined therapy of arrhythmias of varying genesis.

[Effect of mebikar on the state of animals under extreme conditions]. / Vliianie mebikara na sostoianie zhivotnykh pri nekotorykh ékstremal'nykh vozdeistviiakh.

A new original tranquilizer mebicar exerts a protective action on some parameters of body function under the influence of extreme conditions (stress, hypoxia). Antihypoxic effect of the drug manifests within a wide dosage range (100-1000 mg/kg) and compares favourably with the effect of sodium hydroxybutyrate. Mebicar does not affect the muscle tone, movement coordination or working capacity of the animals. It is suggested that the normalizing action of mebicar as tranquilizer and antihypoxic agent may be related to its involvement in metabolism.