BIOCHEMICAL STUDIES ON THE NOOTROPIC DRUG OXIRACETAM IN BRAIN

Abstract

The aim of this work was to study the effects of the nootropic drug oxiracetam, on lipid metabolism in rat brain. Twenty-month-old rats and spontaneous hypertensive (SHR) rats with cerebrovascular lesions were used, which showed an impaired learning and memory rate if challenged with behavioral tests. Oxiracetam improves the in vitro and in vivo synthesis of phosphatidylcholine (PhC) and phosphatidylethanolamine (PhE) impaired by aging, when respectively added to the incubation medium or administered subacutely to animals. SHR rats drinking saline, and with cerebrovascular lesions, have a reduced choline incorporation into cerebral phospholipids and an increase of arachidonic acid release from the same lipids if compared to SHR rats (without cerebrovascular lesions) drinking water. They also show a decreased incorporation rate of arachidonic acid into PhC, PhE, and PhC plasmalogen and PhE plasmalogen. If oxiracetam is chronically administered (200 mg/kg/day for 14 weeks) a significant variation in the incorporation of both precursors takes place. In the first 2 h after the intracerebroventricular (i.c.v.) injection of choline and arachidonic acid the values are comparable to those observed in SHR rats with lesions; at longer time intervals, however, the rates of incorporation are similar and even better than those of SHR rats without lesions. Since the drug does not seem to influence the incorporation of the precursors in the first 2 h after their administration, we may assume that oxiracetam acts on the turnover of the phospholipids more than on their rate of synthesis from injected precursors.