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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.