RESUMEN
Based on the authors' previous data showing that the lipophylic cethyl group promotes the penetration of amino acids through the blood-brain barrier, proline cethyl ester was synthesized and studied as a neuropharmacological tool. The substance administered to rats systemically (intraperitoneally) was shown to be able to provoke a deep amnesia when tested by the conditioned avoidance performance. Piracetam abolished the amnestic effect of proline cethyl ester while sodium hydroxybutyrate administered in the dosage range provoking the nootropic effect did not change that amnesia. The data suggest that proline may be considered as one of the possible endogenous amnestic factors. The close structural similarity of the piracetam cyclic fragment to proline, which resulted in their competition, appears to be one of the reasons for piracetam antiamnestic activity.
Asunto(s)
Memoria/efectos de los fármacos , Piracetam/farmacología , Prolina/análogos & derivados , Pirrolidinonas/farmacología , Animales , Ratones , Prolina/antagonistas & inhibidores , Oxibato de Sodio/farmacologíaRESUMEN
In examining the content of free ammonia, glutamine and some free amino acid s in the brain tissue of mice under normal conditions, in hypoxia and under the effect of succinic acidsemialdehyde, in hypoxia there was revealed a marked increase in comparison with the normal conditions) of the content of free ammonia, and alpha-alanine, a reduction of glutamine; there was also a slight elevation in the content of gamma aminobutyric acid and no changes in glutamic and asparagic acid content. In case of pretreatment with succinic acid semialdehyde the content of free ammonia, glutamine and alpha-alanine in hypoxia approached the normal value. One of the possible mechanisms of the antihypoxic effect of succinic acid semialdehyde was transformation of this compound as a results of which there occurred synthesis of glutamic acid and glutamine leading to detoxication of free ammonia accumulating in the brain tissue in hypoxia.
Asunto(s)
Aminoácidos/metabolismo , Amoníaco/metabolismo , Encéfalo/metabolismo , Glutamina/metabolismo , Hipoxia/metabolismo , Succinatos/farmacología , Alanina/metabolismo , Animales , Ácido Aspártico/metabolismo , Encéfalo/efectos de los fármacos , Glutamatos/metabolismo , Hipoxia/tratamiento farmacológico , Ratones , Succinatos/uso terapéutico , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Preliminary injection of succinic semialdehyde into animals in experiments with hypoxia led to a lower concentration of free ammonia in their brain tissues than in control experiments in which the compound was not given. The enzyme system of the liver tissue catalyzes the oxidation of NAD-H-2 by succinic semialdeyde and its dervitives with a free adelhyde group.The conversion of succinic semialdeyde and its derivatives in the liver tissue leading to the formation of the oxidized form of NAD,which is deficient in hypoxia, and the prevention of accumulation of free ammonia in the brain tissue by preliminary administration of succinic semialdehyde are the possible mechanisms of the antihypoxic properties of succinic semialdehyde and its derivatives.