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The protective effect of piracetam against PGF2 alpha-impaired cerebral resistance to hypoxia was investigated by EEG study in relaxed and artificially ventilated cats. Asphyxic anoxia was performed after 5 min of intracarotid (i.c.) or i.v. infusion of 10 micrograms/kg/min PGF2 alpha before and 30 min after piracetam (100 mg/kg i.v.). The following parameters were determined: cortical resistance (CRs)--as time between stopping the ventilation and the extinction of EEG; cortical recovery (CRc) - as time between restitution of ventilation and reappearance of brain activity; anoxia resistance index (ARI) - as the ratio between these two parameters (CRs/Crc). Both the i.c. and i.v. infusion of PGF2 alpha led to a significant decrease in CRs and lengthening of CRc which resulted in a decrease in ARI. Piracetam reverses the PGF2 alpha-induced changes in asphyxic anoxia. The possible mechanism of piracetam's effect and the probable therapeutic value of the latter are considered.

In connection with some contradictions in the electroencephalographic data for piracetam, further investigations have been carried out to study its effect on the spontaneous and evoked EEG in intact cats after single and a 10-day administration of the drug. On the basis of analysis of the electroencephalogram using an ISEMA frequency-amplitude analyser, the values of the frequency ranges and those of the mean amplitude were averaged by use of FACOM computer. The results from our experiments indicate that no visual differences in the spontaneous and evoked EEG after piracetam administration have been observed. The spontaneous activity after the 10-day treatment with 1000 mg/kg i.m. quantitatively shows an increase of the fast frequencies (beta and alpha waves), increase of the mean amplitude, and increase of the evoked activity after visual and sound stimulation. An involvement of deep structures in performing the effect of piracetam is admitted as well as kind of "augmentation" of the cerebral bioelectrical activity.

The anti-hypoxic effect of piracetam was studied using the following experimental methods: hypobaric and anoxic hypoxia in mice, complete ischemia by decapitation in mice, incomplete ischemia by bilateral carotid occlusion in rats and hemic hypoxia in rats. Cinnarizine and vinpocetine were used as reference drugs. In hypobaric hypoxia, anoxic hypoxia, and complete ischemia by decapitation the interaction of piracetam with the effect of prostacyclin (PGI2) was investigated. Piracetam showed anti-hypoxic effect in all the methods used. Its effect was greater than that of cinnarizine and similar to that of vinpocetine. Piracetam potentiated the effect of PGI2 shifting the anti-hypoxic dose-response curve of PGI2 to the left.

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 effect of piracetam (100 mg/kg i.v.) on general and local depression of the cortical bioelectrical activity was studied in acute experiments on cats. Asphyxic anoxia and hypoventilation hypoxia were used as models of general depression. Local depressions were caused by topical application of potassium chloride (KCl), adenosine monophosphate (AMP) and pentobarbital on the cortex. In the models of general depression piracetam increased cortical resistance to hypoxia and accelerated the recovery of the cortical bioelectrical activity. In KCl- and AMP-induced depressions piracetam diminished their degree and duration and completely protected the cortex against pentobarbital-caused depression.

The effect of piracetam on the excitability of the brain has been examined in cats by electrophysiological approaches: spontaneous electrocorticogram (ECoG), visual evoked potentials (VEPs) and their recovery cycles in some brain structures (visual and associative cortex, lateral geniculate body, centrum medianum thalami and mesencephalic reticular formation). Piracetam (100 mg/kg i.v.) increased the spectral power of ECoG and particularly in the associative cortex for the frequency bands of 10-12 and 19-22 Hz. Piracetam decreased the early components and facilitated the late components of VEPs predominantly in the associative cortex. Changes were found in the recovery cycles too, namely, facilitation and shortening of recovery in all structures studied except in lateral geniculate body. The data suggest that piracetam acts as a non-specific activator on the excitability thus optimizing the functional state of the brain.

The effect of piracetam has been studied in experimental models of the inflammatory process--the models of rat's paw oedema and intraperitoneal formalin ascites for the exudative phase and the cotton pellet model for the proliferative phase. Piracetam restricts the development of the exudative and proliferative phases of the inflammatory process. The degree of this reduction in the models used is similar to that observed after treatment with known antiinflammatory drugs. On the basis of data in the literature, the effects observed are explained by the action of piracetam upon cell-membrane permeability and the oxidation-reduction processes in the cell.

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.

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.