Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABAA and muscarinic receptors induced by cycloheximide.
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.
Nabeshima
T
T
Department of Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Tohyama
K
K
Murase
K
K
Ishihara
S
S
Kameyama
T
T
Yamasaki
T
T
Hatanaka
S
S
Kojima
H
H
Sakurai
T
T
Takasu
Y
Y
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
D002491:Central Nervous System Agents; D011760:Pyrrolidinones; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; C058876:nefiracetam; C036466:aniracetam; D003513:Cycloheximide; D012601:Scopolamine