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.
Nabeshima
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Noda
Y
Y
Tohyama
K
K
Itoh
J
J
Kameyama
T
T
D000647:Amnesia / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009118:Muscimol / Q000494:pharmacology; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology*; D010852:Picrotoxin / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001640:Bicuculline; D002491:Central Nervous System Agents; D009118:Muscimol; D010852:Picrotoxin; D011760:Pyrrolidinones; D005680:gamma-Aminobutyric Acid; C058876:nefiracetam; C036466:aniracetam