Effect of nebracetam on nicotinic and muscarinic acetylcholine receptors expressed in Xenopus oocyte by injecting exogenous mRNA.
Using voltage- and current-clamp methods the effects of nebracetam 4-aminomethyl-1-benzylpyrrolidine-2-one hemifumarate, WEB 1881 FU, CAS 118607-07-1), a new agent with nootropic property, on the nicotinic (nAChRs) and muscarinic acetylcholine receptors (mAChRs) were studied, which were expressed in Xenopus oocytes by injecting E. electricus mRNA and rat brain mRNA, respectively. Simultaneous application of nebracetam (0.03-2 mmol/l) with acetylcholine (ACh) (0.01-1 mmol/l) inhibited the ACh-responses of both nAChRs and mAChRs, whereas preapplication of these concentrations of nebracetam for 30 s to 1 min potentiated such inhibition. A simple competitive inhibition model for the effects of both drugs simultaneously applied yielded the inhibition constant, K1 of 0.419 and 0.212 mmol/l for nAChRs and mAChRs, respectively, indicating that the action on mAChRs is a little more potent than on nAChRs. Nebracetam induced a concentration-dependent slight increase in inward currents on mAChRs but not on nAChRs. It is suggested that the direct effects of nebracetam on nAChRs and mAChRS, which were induced only by a rather high concentration, as compared with the clinically expected plasma level, may be a contributing factor to the clinical effectiveness of the drug only if there is some critical change in the sensitivity to the drug.
Aoshima
H
H
Department of Chemistry, Faculty of Liberal Arts, Yamaguchi University, Japan.
Shingai
R
R
Ban
T
T
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004594:Electrophysiology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism*; D010277:Parasympathomimetics / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics; D014982:Xenopus laevis
D010277:Parasympathomimetics; D011760:Pyrrolidinones; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D000109:Acetylcholine; C056640:nebracetam