Brain Entry and Direct Central Pharmacological Effects of the Nootropic Drug Oxiracetam

: Oxiracetam administered systemically to rats as a 14C radiolabelled drug (200 mg/kg p.o. or 100 mg/kg intra-artery) enters the brain and is found unmetabolized above all in some of the brain areas functionally involved in the modulation of cognitive processes. Among the brain areas examined, the largest amount of compound was recovered in septum, followed by hippocampus; a smaller amount was found in cerebral cortex and striatum. 14C oxiracetam administered directly into the lateral ventricles of the brain presented a similar pattern of distribution, indicating that the tropism of the drug for the above brain areas does not depend on its route of administration. The amounts of oxiracetam that could reach the brain after systemically administered pharmacologically active doses were also estimated. These amounts (1.9 to 19 nmols/rat) were delivered through a permanently implanted cannula, into the lateral ventricles of the brains of conscious, freely moving rats. In this experimental condition oxiracetam dose-dependently antagonized the amnesia induced by scopolamine (0.66 mg/kg s.c.). The above findings clearly indicate that oxiracetam enters the brain and directly exerts its pharmacological activity there.