Effects of DM-9384 in a model of amnesia based on animals with GABAergic neuronal dysfunctions

The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DM-9384), a cyclic derivative of GABA, were investigated and compared with those of aniracetam in an animal model of amnesia, using a passive avoidance task with animals that have GABAergic neuronal dysfunctions. Pre- and post-training administration of DM-9384 and aniracetam ameliorated bicuculline-induced amnesia, as indicated by parameters such as % retention and step-down latency. DM-9384 ameliorated picrotoxin-induced amnesia when administered pre-training, but not when administered post-training. Aniracetam failed to improve the picrotoxin-induced amnesia. DM-9384 displaced [3H]muscimol binding to GABAA receptors (-log IC50 = 8.07 M; Hill value = 0.23 +/- 0.04), but failed to displace about 20% of the specific muscimol binding, whereas aniracetam showed only a weak effect (-log IC50 = 3.63 M; Hill value = 0.37 +/- 0.06). From these results, it appears that DM-9384 ameliorated the GABA antagonist-induced amnesia by interacting with some GABAA receptors directly and/or indirectly.