A study of the mechanisms for antiaggregant activity of pyrrolidone derivatives in rats with chronic hyperglycemia.

In rats with chronic alloxan-induced hyperglycemia, pramiracetam and phenylpiracetam (but not piracetam) had a strong antiaggregant effect that was mediated by various mechanisms of platelet aggregation modulation. The effect of pramiracetam is mainly realized via the inhibition of thromboxane A2 metabolism, while activity of phenylpiracetam is primarily associated with a normalizing effect on function of constitutive NO synthase in platelets and vascular endothelium.

[Study of acetylsalicylic acid role in the potentiation of antiamnesic and neuroprotective properties of piracetam in rats with alloxan diabetes].

It has been established that prolonged alloxan-induced hyperglycemia in rats potentiates amnesic properties of scopolamine hydrobromide. It was characterized by shortening of the latent period by 44% (p<0,01) and by 47,7% (p<0,05) after 24 hours and on the 20th day of conditioned passive avoidance test. This effect was accompanied by increase in oxidative modification of proteins and nitric oxide synthesis in the cerebral cortex. Along with this, a significant enhancement of ADP- and collagen-induced platelet aggregation was observed. These processes may play the leading role in the development of cognitive deficit in diabetes. Meanwhile, co-administration of piracetam with acetylsalicylic acid was accompanied by an expressed antiamnetic potential - the reduction of early markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (p<0,05) and late markers of proteins degradation (ketonephenylhydrazones, KPH) by 23,8% (p<0,001) was noted. This combination was 15,7% (p<0,05) more active than piracetam according to the effect upon KPH. NO2-/NO3- level was also decreased by 30,3% (p<0,05) in comparison with alloxan-diabetic rats. The significant anti-platelet effect was observed: degree of collagen-induced platelet aggregation was reduced by 56,8% (p<0,01), ADP (5 µmol/l)-induced - by 31,7% (p<0,01), ADP (20 µmol/l)-induced - by 47,3% (p<0,01) as compared to the hyperglycemic rats. Such an increase in nootropic activity of piracetam may be assumed to be directly related to the ability of acetylsalicylic acid to improve microcirculation in the ischemic areas of the brain in diabetes and probably to its neuroprotective potential.

[Platelet hyperreactivity and antiaggregatory properties of nootropic drugs under conditions of alloxan-induced diabetes in rats].

The effects of nootropic drugs (noopept, pentoxifylline, piracetam, pramiracetam, Ginkgo biloba extract, entrop, cerebrocurin and citicoline) on platelet aggregation in rats with experimental diabetes have been studied. It is established that all these drugs exhibit an inhibitory action of various degrees against platelet hyperreactivity under conditions of chronic hyperglycemia. The maximum universality of the antiaggregatory action is characteristic of pramiracetam, entrop and Ginkgo biloba extract.