[Experimental studies of the effect of a single administration of nootropil in acute imipramine poisoning].
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Biomedical subjects
Publications and source records attributed to M Nikolova.
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The authors examined the effect of the ortonic acid in comparison with several preparations from various pharmacologic groups on models of complete ischemia, obtained by decapitation and hypobaric hypoxia in mice. The ortonic acid showed strong anti-hypoxic effect in these two models. The results revealed that the strongest effect manifested the ortonic acid, followed by vinponcetine and cinarizine, in mice with hypoxia, induced by decapitation and by the method of hypobaric hypoxia. Hexobarbital-sodium and papaverine showed comparatively weaker effect, but xantional nicotinate - the slightest. A wide spectrum od drugs, known by experimental and clinical data as antihypoxic drugs allowed the authors to accept the models as relative and the conclusion for the effect of the ortonic acid was considered as significant. They assume that vascular and metabolism effect participates in the mechanism of the antihypoxic action of the ortonic acid.
In view of the interesting problem of the correlation between the functional cerebral activity and cerebral blood circulation, as well as the controversy in the literature concerning the effects of tranquilizers on cerebral blood circulation, the effects of the daily tranquilizer Lonetyl on the spontaneous cerebral bioelectrical activity and cerebral haemodynamics have been studied. According to rheoencephalographic data, Lonetyl is found to reduce cerebral vascular tone, which is manifested by decreased values of the relative share and the dicrotic index, the maximum effect being observed between the 15th and 30th min. The changes in the EEG consist in significant increase of the alpha- and theta-activity, with maximum effect on the 15th min, increased mean frequency and decreased mean amplitude. Synchronization of the cerebral bioelectrical activity is observed after the 30th min.
The influence of piracetam (2-oxo-1-pyrrolidine-acetamide, Pyramem) on the cerebral circulation and brain bioelectrical activity of cortex and mesencephalic reticular formation (RF) was studied in acute experiments on cats which were encéphale isolé preparations. The methods of local cerebral rheoencephalography (REG) and electroencephalography (EEG) were used. The following REG parameters were assayed: anacrotic section of the curve and its relative part, amplitude and duration of the wave. The arterial blood pressure was followed continuously. The results show that upon piracetam administration (150 mg/kg i.v.) an improvement of the REG parameters of the cortex and RF is observed-an increase of the amplitude and decrease of the values of the anacrotic section of the curve and its relative part. The changes observed indicate a cerebro-vascular resistance decrease and give indirect evidence of cerebral blood volume increase. EEG data are characterized mainly by an increase of alpha-waves, both of cortex and RF. Suggestions for possible mechanism of action of piracetam are made.
The effect of piracetam (2-oxo-1-pyrrolidine-acetamide, Pyramem) on the local cortical cerebral blood flow (CBF) and oxygen balance in the brain was studied on cats anesthetized with ether-chloralose. The changes in local CBF were registered by means of the thermistor thermoclearance technique. pO2 and pCO2 were determined in blood samples from the femoral artery and superior sagittal sinus and arterio-venous differences of O2 and CO2 partial pressures (AVD-O2 and AVD-CO2) were calculated. The experiments were made on normoxic animals and on animals with slight hypoxia. Piracetam administration (100 mg/kg i.v.) leads to an increase in local cortical CBF corresponding to a change in the specific thermoconductivity of the brain of 0.6 . 10(-4) cal . cm-1 . sec-1 . degrees C-1. This effect is observed in 84% of the experiments with normoxia (arterial pO2 96.0 +/- 21.0 mm Hg) and in 40% of the experiments with slight hypoxia (arterial pO2 59.9 +/- 6.0 mm Hg). Changes in AVD-O2 and AVD-CO2 are not observed. Most probably the increase in CBF does not participate in the mechanism of the protective action of piracetam in hypoxia.
In acute experiments on cats under urethan anaesthesia and on dogs under chloralose-urethan narcosis the effect of the cinnarizine analogue Aligeron on local cortical cerebral blood flow (local CBF) and internal carotid blood flow was studied. The local CBF was recorded by means of a thermoclearance method using thermistor transducers. In addition the cortical pH and the arterial blood pressure were registered. For determination of internal carotid flow the flowmetric method was used accompanied by a simultaneous registering of heart rate and arterial blood pressure. Cinnarizine and papaverine were used as reference compounds. The results obtained show that Aligeron increases both the internal carotid flow (with 64% in a dose of 5 mg/kg) and the local CBF (with 30% in a dose of 1 mg/kg and 40% at 5 mg/kg). This effect is higher and longer-lasting than those of cinnarizine and papaverine.
The authors examined resorption and distribution of the preparation pyramem (2-oxo-1-pyrrolidinacetamide), synthesized by RICPI and the obtained data were compared with literary data on the preparation pyracetam. Gas chromatographic method, described in the literature, was introduced for determination of concentration of pyracetam in plasma using some modifications. The obtained results and the pharmacokinetic parameters, estimated on the basis of the results, showed good coincidence with those reported in literature. The established quick resorption, the course of plasma curves after oral and venous application and biologic half-life of pyramem in rats gave foundation to conclude that the synthesized by RICPI 2-oxy-1-pyrrolidinacetamide was identical with preparation pyracetam.
The following methods were used: neuropharmacologic study according to the a modified method of Nikolova, Daleva, orientation reaction according to Boissier and Simon, "open field" according to Fontenay et al. and actographic study. The data from "the free" observation suggested clearly a manifested central stimulating effect of aligeron. The data from the actographic study were similar, which showed an increased motor activity in mice and rats, given doses of 1/100-1/4 of LD50. The stimulating action of the preparation was observed in doses of 1/8-1/6 of LD50 during the experimental procedure "open field". The preparation inhibited orientation reaction in mice. Cinnarizine inhibited the examined indices, obtained by all tests. The complex of the used methods allowed to make an inference that aligeron had central stimulating effect, weaker in smaller therapeutic doses and more manifested in higher doses. Cinnarizine had weak depressive effect.
Virological and serological studies of an epidemic disease in Bulgaria, 1975, were carried out. Epidemiologically, clinically and pathomorphologically, the disease simulated almost all known forms of poliomyelitis, acute stem encephalitis, encephalomyocarditis and aseptic meningitis. The studies completely rules out the participation of polioviruses and provided comprehensive evidence for the etiological role of a peculiar enterovirus subsequently identified as enterovirus (EV) type 71 known in the literature since 1974. Altogether, in 1975 and 1976 from 65 cases of poliomyelitis-like disease (PLD) 92 strains of EV71 were isolated, including 37 strains from the brain and medulla, 1 from the cerebrospinal fluid, 10 from mesenterial lymph nodes and tonsils and 44 from faeces. In addition, in 282 convalescent cases of the disease, diagnostic seroconversion or high titers of antibody to this virus were demonstrated. The most successful virus isolation was achieved by inoculation of green monkey kidney cell cultures and newborn white mice. Bulgarian strains of enterovirus 71 regularly caused paralysis in monkeys and morphological poliomyelitis-like lesions in their CNS, and paralysis and myositis with Zenker necrosis in newborn white mice, cotton rats, Syrian hamsters, and 3-week-old cotton rats. The diseased rodents had much more virus in their mucles than in brains.
Various well-known agents with a favourable influence on cerebral circulation were used as a basis for creating new methods to asses the effects on this vascular region in experimental animals. A technique was worked out for radiocirculography and simultaneous radiometry, as well as for scanning and simultaneous radiometry of cat brain. Radiocirculography, followed by scintigraphy, proved to be among the best methods used for assessment of the effect of As2 on cerebral circulation. Simultaneous radiometry with the methods mentioned above had only orientational value. Radiocirculographic and scanning data after application of As2 in a dose of 10 mg/kg are close to those for nicotinic acid in a dose of 1 mg/kg. Similar to the data of the isotopic methods after application of As2 in a dose of 5 mg/kg are the results obtained with 5 mg/kg cinnarizin, which suggests a similar machanism of action.
The effect of As2 and Cinnarizin on cerebral circulation is studied on rabbits using the method of local cerebral rheography. Rheoencephalograms (REG) are recorded from the following brain structures; sensomotor cortex, substantia alba, poseterior hippocampus amygdala; nucleus caudatus and coliculus superior. Arterial blood pressure and ECG are studied simultaneously. Qualitative and quantitative analysis of the REG wave is made. Quantitative analysis involves the calculation of the following parameters: amplitude, anacrotic section of the curve and its relative part, spreading time and dicrotic index. The complex of REG-changes under the effect of the two drugs is very similar and suggests dilatation of the cerebral blood vessels. The difference is in the time of occurrence of the maximum effect: 5th min for As2 and 45th min for Cinnarizine.
By means of the methods of local cerebral rheoencephalography (REG) and electroencephalography (EEG) the effect of piracetam (1-acetamide-2-pyrrolidone, Pyramem) on cerebral circulation and brain bioelectrical activity was studied in acute experiments on dogs. The following REG parameters were assayed: anacrotic section of the curve and its relative part, amplitude and dicrotic index. The influence of the preparation on the spontaneous EEG was studied by means of surface electrodes, pH, pO2, and pCO2 were determined in blood samples from femoral artery and superior sagittal sinus and arterio-venous differences of O2 (AVD-O2) and CO2 (AVD-CO2) were calculated. The arterial pressure and ECG were followed continuously. The results showed that after piracetam administration (100 mg/kg i.v.) an improvement of the REG parameters is observed: increase of the amplitude and decrease of the values of the relative part and dicrotic index. The changes observed indicated cerebro-vascular resistance decrease and increase of the cerebral blood volume. The AVD-O2 increased and the negative AVD-CO2 decreased. The EEG data indicated an improvement in the functional state of the brain cortex. Suggestions as to mechanism of piracetam effect and the usefulness of the methods were made.
It was noted that under the conditions of industrial raising of adult birds the epizootic of Salmonella heidelberg could assumme an acute course with a clinical manifestation. After its short-term acute manifestation the infection acquired a protracted course. Mortality correlated directly with the age of the birds. Isolated and identified were a total of 117 Salmonella heidelberg strains from carcasses, cloacal samples, eggs, and litter. Regardless of the short-term Salmonella harbouring the deep litter was shown to predispose to reinfections. The isolation of eight strains of S. heidelberg from the egg shell and the yolk of freshly laid eggs as well as the negative microbial findings in one- and two-fold fumigated eggs corroborate the idea of the additional entering of Salmonella organisms through the shell. These also point to the fact that fumigation carried out up to the third hour following laying may contribute to the raising of disease-free broilers. Treatment with furazolidon and chloramphenicol in combination or the application of salmocid at the rate of 250 milligram microgram of feed in the course of ten days suppresses the acute manifestation of the disease and restores the productivity of birds, having no effect on the harbouring of the infection in the flock.
A group of original symmetrical and asymmetrical piperazine compounds containing ester function have been synthesized and pharmacologically characterized. All compounds are pharmacologically active. Some relationships between their chemical structure and biological activity are discussed. Analgesic and coronary dilatory and especially spasmolytic effects are marked for all asymmetrical esters. A number of the compounds are interesting for further investigations relative to their possible application in medical practice.
The effect of the compound AS2 (N'-benzhydryl, N''-allylpiperazine dihydrochloride) on the central and peripheral mechanisms of vascular tone regulation is studied. Six series of experiments on cats are carried out. The effect of the compound is tested on a model of central-hypertensive reaction, on the spontaneous bioelectrical activity of the renal nerve, on the transmission of excitation to the upper cervical ganglion and the ganglia of the solar plexus. Experiments are made to study its adrenolytic a-d myotropic properties. Cinnarizine is tested as control. The results show that the compound AS2, similar to Cinnarizine, affects the central and peripheral mechanisms of vascular tone regulation. In small doses (1-5 mg/kg) AS2 manifests poor myotropic properties. Administration of the drug in doses of 10-20 mg/kg results in considerable inhibition of the vasomotor centres, brief disturbances in the excitation transmission in the sympathetic ganglia and slight inhibition of adrenergic transmission.
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