[Biochemical studies of oxiracetam (CT-848) on cholinergic neurons].
Effects of oxiracetam on cholinergic neurons were investigated by biochemical methods. 1) Oxiracetam did not inhibit 3H-QNB binding in the cerebral cortex and hippocampus. 2) In the 3H-QNB binding study, oxiracetam did not change the inhibition-concentration curve for the muscarinic agonist carbachol and had no effect on GppNHp-induced inhibition of oxotremorine binding. 3) Oxiracetam (10-100 microM) enhanced K(+)-induced ACh release from slices of rat hippocampus. 4) In the in vitro perfusion studies, oxiracetam (10-100 microM), but not aniracetam and piracetam, enhanced choline-acetyltransferase (ChAT) activity in the hippocampal slices. 5) Repeated administration of oxiracetam (100 or 500 mg/kg, p.o., once daily) to old rats significantly enhanced ChAT activities in the cerebral cortex, hippocampus and striatum, while it did not influence the Bmax and Kd for 3H-QNB binding in the hippocampus. 6) Oxiracetam did not affect the acetylcholinesterase activity in mouse brain homogenate. These results suggest that oxiracetam enhances precholinergic functions.
Mochizuki
D
D
Exploratory Research Laboratories, Toyo Jozo Co., Ltd., Shizuoka, Japan.
Sugiyama
S
S
Shinoda
Y
Y
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D010095:Oxotremorine / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism
D011759:Pyrrolidines; D011950:Receptors, Cholinergic; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine; C040619:oxiracetam