Effects of GABA and piracetam on the development of experimental cerebral infarction in rats and platelet aggregation in patients with cerebrovascular disorders

GABA and Piracetam caused the improvement of the morphological state of cerebral infarction, due to intracarotid infusion of Arachidonic acid. The effect of GABA was more pronounced. The diminishing of antiaggregatory effect of Piracetam arose in patients with acute cerebrovascular disturbances, compared with the donor group. In contrast, the antiaggregatory activity of GABA increased in the patients group. The improvement of cerebral circulation under influence of GABA can be ascribed to its rheological changes.     

Characteristics of the antihypoxic action of piracetam

Pyracetam was found to inhibit free-radical lipid peroxidation, slow oxygen consumption in the liver mitochondria and increase hemoglobin oxygen-binding properties. It is assumed that the ability of pyracetam to inhibit lipid peroxidation is a mechanism which determines its antihypoxic effect.     

Mechanism of permissive prostacyclin action in cerebrovascular smooth muscle

Prostacyclin permissively allows increased cAMP and cerebral vasodilation to hypercapnia in piglets. The prostacyclin receptor (IP) is coupled to phospholipase C (PLC) in piglet cerebral microvascular smooth muscle cells (SMC). We hypothesize that inhibition of PLC blocks the permissive action of IP receptor agonist, iloprost, and direct activation of PKC substitutes for the IP receptor agonist in SMC. SMC cAMP production was measured at normal pHi/pHo and with reduced pHi/pHo in the absence and presence of iloprost (100 pM). Half of the cells were pretreated with U73122, the PLC inhibitor, which decreased the basal IP3 and blocked the increase in IP3 caused by iloprost. Without iloprost, decreasing pHi/pHo increased cAMP production (40%). With iloprost, the cAMP response to acidosis increased to over 80%. U73122 prevented accentuation of the cAMP response by iloprost. Phorbol myristate acetate augmented the response to acidosis similarly to iloprost. These data suggest IP agonists augment the cAMP response to acidosis via coupling through PLC to activate PKC.     

Metabolic features of the adaptive effect of delta-sleep inducing peptide and piracetam under hyperoxic conditions.

Adaptive effects of delta-sleep inducing peptide (DSIP, 12 microgram/100 g body weight, single intraperitoneal injection) and piracetam (3 mg/100 g body weight, daily intraperitoneal injection for 3 days) are manifested via differential changes in neurotransmitter amino acids (GABA, glutamate, aspartate), modulation of transport ATPase activity, and decreased accumulation of lipid peroxidation products (conjugated dienes, malonic dialdehyde, Schiff bases) in various fractions of neuronal membranes (myelin, synaptic and mitochondrial membranes) in the sensomotor cortex of rat brain. Under hyperbaric oxygenation (0.3 MPa for 2 h), the combination of DSIP and piracetam enhanced the protective effect of each compound.     

Habituation of caddies Chaetopteryx villosa larvae to vibrational stimulus and effect of piracetam on it

Habituation to a vibrational stimulus was studied in intact caddies Chaetopteryx villosa Fabr. of the last age before pupation and of the larvae placed for 72 h into pyracetam solution (100 mg/l). The vibrational stimulus was shown to produce a passive-defensive reaction: the caddies were pulled into the house and stood still. In the course of the experiment the time of stay in the house decreased statistically significantly in both groups. Pyracetam did not affect the defensive reaction at the initial moment of the first vibrational stimulus, so both in the experimental and in the control groups the number of contracted larvae was equal and all of them remained in the house for the first seconds of vibration. However, the compound increased the number of larvae that did not respond to the next vibrational stimulus and decreased the number of larvae that remain in the house throughout all 10 s of action by accelerating on the whole the habituation. Hence, on this model, the mnemotropic effect of the standard nootrope has been realized, which earlier was established by other methods in mammals, the lower vertebrates, and the higher invertebrates. This indicates that this model also is perspective for comparative studies of effect of nootropic substances on the higher nervous activity.     

Contrasting effect of piracetam and proline on the release of 3H-D-aspartic acid from the cerebral cortical synaptosomes of rats

Piracetam (at concentrations of 10(-6) and 10(-5), but not 10(-4) and 5 X 10(-4) M) decreased K+-stimulated 3H-D-aspartate release. Proline enhanced K+-stimulated D-aspartate release, and its effect was antagonized by piracetam at a concentration that had no effect on K+-stimulated release. Quisqualic acid attenuated K+-stimulated D-aspartate release, with the effect antagonized by GDEE. GDEE also blocked the effect of piracetam, but not proline. The data are discussed in terms of the role of excitatory amino acid neurotransmission in the mechanisms of amnestic and antihypoxic piracetam action.     

Effect of piracetam derivatives on antibody formation

Immunomodulatory effects of piracetam and a number of its derivatives were studied in mice. It was shown that multiple injections of such substances at a dose of 50-200 mg/kg change the amount of antibody-forming cells in the spleen of animals immunized with sheep red blood cells. The dose of 200 mg/kg was the most effective one, with the direction of immunomodulatory activity depending on the chemical composition of the compounds. Thus joining of phenol radical to piracetam molecule strengthened immunosuppression, and vice versa insertion of hydrazide group led to stimulation of antibody formation. It is stressed that immunosuppressive effect of piracetam must be taken into consideration during the clinical use of the drug.     

Individual sensitivity of Wistar rats to piracetam

Effects of repeated piracetam (PIR) injections in a dose of 40 and 250 mg/kg/day on the learning in Water rats were studied. It has been found that character of the effects depends on typological features of the animals. Rats with strong predominance of excitation (choleric type) showed low sensitivity to PIR. Small dose of PIR provoked clear negative effect in rats with relative balance of the basic nervous processes: excitation and inhibition (sanguine and phlegmatic types). Despite of expressed activation of associative process, it complicated integrative activity. Small dose of PIR showed anxiolytic and psycho-stimulant actions only in initially unlearned rats characterized by high level of fear. Large dose of PIR had negative influence on the learning process in all animals, irrespective of typological features. Thus, the results of this study allow to suppose that the individual sensitivity of an animal to action of a pharmacological medication is caused by morpho-functional and neurochemical intraspecific heterogeneity.     

Habituation of caddies Chaetopteryx villosa Fabr. Larvae to vibrational stimulus and effect of piracetam on it

Habituation to a vibrational stimulus was studied in intact caddies Chaetopteryx villosa Fabr. of the last age before pupation and of the larvae placed for 72 h into piracetam solution (100 mg/l). The vibrational stimulus was shown to produce a passive-defensive reaction: the caddies were pulled into the house and stood still. In the course of the experiment the time of stay in the house decreased statistically significantly in both groups. Piracetam did not affect the defensive reaction at the initial moment of the first vibrational stimulus, so both in the experimental and in the control groups the number of contracted larvae was equal and all of them remained in the house for the first seconds of vibration. However, the compound increased the number of larvae that did not respond to the next vibrational stimulus and decreased the number of larvae that remain in the house throughout all 10 s of action by accelerating on the whole the habituation. Hence, on this model, the mnemotropic effect of the standard nootrope has been realized, which earlier was established by other methods in mammals, the lower vertebrates, and the higher invertebrates. This indicates that this model also is perspective for comparative studies of effect of nootropic substances on the higher nervous activity.     

Mechanism of the radioprotective effect of cysteamine

The radioprotective effect of cysteamine combined with the modification of the chromatin state by sodium butyrate has been studied using V-79 and CHEL lines of Chinese hamster cells and HeLa cells. Sodium butyrate enhances the chromatin sensitivity to nucleases and removes the radioprotective effect of cysteamine as measured by the yield of cells with chromosome aberrations. As is indicated by changes in the intensity of fluorescence of the DNA-ethidium bromide complex, measured by laser flow cytometry, the protective agent decreases the binding of the dye with both irradiated and nonirradiated DNA whereas ionizing radiation and sodium butyrate increase thereof. It is concluded that the radioprotective effect of cysteamine depends in its ability to reduce the susceptibility of DNA to nucleases.