S. Watabe et al., DM-9384, A NEW COGNITION-ENHANCING AGENT, INCREASES THE TURNOVER OF COMPONENTS OF THE GABAERGIC SYSTEM IN THE RAT CEREBRAL-CORTEX, European journal of pharmacology, 238(2-3), 1993, pp. 303-309
DM-9384 (nefiracetam) imethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide
), a pyrrolidone derivative (or a cyclic derivative of gamma-aminobuty
ric acid (GABA)), is a newly developed nootropic (or cognition-enhanci
ng) agent. In the present study, we examined the biochemical effect of
DM-9384 on GABAergic neurons in adult rat brains. DM-9384, when admin
istered orally at a daily dose of 10 mg/kg for 7 days, significantly i
ncreased GABA turnover and glutamic acid decarboxylase activity in the
cortex and hippocampus, and stimulated Na+-dependent high-affinity GA
BA uptake in cortical synaptosomes. In in vitro experiments, the K+-ev
oked release of [C-14]GABA from cortical slices was markedly increased
by low concentrations (10(-8), 10(-9) M) of DM-9384. The binding of G
ABA(A) and benzodiazepine to their receptors in the brain was not affe
cted by DM-9384 (10(-10)-10(-3) M). ne results suggest that DM-9384 in
creases the turnover of components of the GABAergic system by influenc
ing presynaptic sites rather than postsynaptic sites.