Anticonvulsant activities of N-benzyloxycarbonylglycine after parenteral administration.
Although glycine does not cross easily the blood-brain barrier, it exhibits at very high doses (10-40 mmol kg-1) a modest anticonvulsant activity. In this study, carbamate derivatives--N-benzyloxycarbonylglycine (Z-glycine) and N,tert-butoxycarbonylglycine (Boc-glycine)--have been compared with glycine. Z-glycine (1 mmol kg-1), but not Boc-glycine, reduces the number of tonic convulsions in the 3-mercaptopropionic and in the bicuculline tests, increases the latency of seizures in the strychnine test and is as active 3 h after administration as sodium valproate 30 min after administration in the maximal electroshock seizure test. Overall, milacemide, a precursor of glycine, and Z-glycine have rather similar anticonvulsant profiles in mice. The lack of Z-glycine affinity for the strychnine sensitive glycine receptor and the strychnine insensitive glycine receptor associated with the NMDA receptor may indicate that Z-glycine acts either via a prodrug mechanism or per se via an alternative mechanism.
Laboratory of Medicinal Chemistry, School of Pharmacy, Catholic University of Louvain, Brussels, Belgium.
D M
DM
Lambert
J H
JH
Poupaert
J M
JM
Maloteaux
P
P
Dumont
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001667:Binding, Competitive; D004597:Electroshock; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007263:Infusions, Parenteral; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018009:Receptors, Glycine / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology
D000927:Anticonvulsants; D018009:Receptors, Glycine; C088043:N-benzyloxycarbonylglycine; C029052:BOC-glycine; D005998:Glycine