Biochemical studies of oxiracetam (CT-848) on cholinergic neurons

Abstract

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 μM) enhanced K+-induced ACh release from slices of rat hippocampus. 4) In the in vitro perfusion studies, oxiracetam (10~100 μM), but not aniracetam and piracetam, enhanced cholineacetyltransferase (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 mouce brain homogenate. These results suggest that oxiracetam enhances precholinergic functions.