title: Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide.
abstract: The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide [DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre- and post-training and pre-retention test administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. Aniracetam, another cyclic derivative of GABA, also showed antiamnesic effects. Scopolamine, a muscarinic ACh receptor antagonist, and the GABA antagonists, picrotoxin and bicuculline, all antagonized the antiamnesic effects of DM-9384. CXM decreased the number of GABAA and muscarinic ACh receptor binding sites. DM-9384 not only inhibited this effect but actually increased the latter. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with GA-BAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.
authors.affiliation: Department of Hospital Pharmacy, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nabeshima
authors.forename: K
authors.initials: K
authors.lastname: Tohyama
authors.forename: K
authors.initials: K
authors.lastname: Murase
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: T
authors.initials: T
authors.lastname: Kameyama
authors.forename: T
authors.initials: T
authors.lastname: Yamasaki
authors.forename: S
authors.initials: S
authors.lastname: Hatanaka
authors.forename: H
authors.initials: H
authors.lastname: Kojima
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: Y
authors.initials: Y
authors.lastname: Takasu
mesh_terms: D000647:Amnesia / Q000139:chemically induced* / Q000517:prevention & control; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology*; D008297:Male; D051379:Mice; D014176:Protein Biosynthesis; D011760:Pyrrolidinones / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000032:analysis / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D002491:Central Nervous System Agents; D011760:Pyrrolidinones; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; C058876:nefiracetam; C036466:aniracetam; D003513:Cycloheximide; D012601:Scopolamine