Synthesis of valproyl-2-pyrrolidinone and its evaluation as a cognitive drug with the ability to modulate acidic amino acids in the brain.
A new pyrrolidinone derivative, valproyl-2-pyrrolidinone (VP), was synthesized, followed by evaluation as a cognitive drug. VP gave rise to a significant protective effect against cerebral anoxia together with a potent prolongation of latency time for the reversal of scopolamine induced transient disruption of the memory of a passive avoidance response in rats. The quantitative experiment using HPLC demonstrated a significant reduction of hippocampal aspartate (Asp) and glutamate (Glu) following the intraperitoneal administration of VP at a dose of 300 mg/kg.
Miyazaki
C
C
Department of Hospital Pharmacy, Nagasaki University Hospital, Japan.
Matsuyama
K
K
Ichikawa
M
M
Goto
S
S
Yamamoto
J
J
D000284:Administration, Oral; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D010205:Pantothenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D005971:Glutamates; D011760:Pyrrolidinones; C064281:valproyl-2-pyrrolidinone; C016030:pantogab; D010205:Pantothenic Acid; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C036466:aniracetam