Lambert D M, Poupaert J H, Maloteaux J M, Dumont P
Laboratory of Medicinal Chemistry, School of Pharmacy, Catholic University of Louvain, Brussels, Belgium.
Neuroreport. 1994 Mar 21;5(7):777-80. doi: 10.1097/00001756-199403000-00010.
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.
尽管甘氨酸不易穿过血脑屏障，但在非常高的剂量（10 - 40 mmol kg-1）时，它表现出适度的抗惊厥活性。在本研究中，将氨基甲酸酯衍生物——N-苄氧羰基甘氨酸（Z-甘氨酸）和N-叔丁氧羰基甘氨酸（Boc-甘氨酸）——与甘氨酸进行了比较。Z-甘氨酸（1 mmol kg-1），而非Boc-甘氨酸，在3-巯基丙酸和荷包牡丹碱试验中减少了强直惊厥的次数，在士的宁试验中增加了癫痫发作的潜伏期，并且在最大电休克惊厥试验中，给药3小时后的活性与丙戊酸钠给药30分钟后的活性相同。总体而言，甘氨酸前体米那西肽和Z-甘氨酸在小鼠中具有相当相似的抗惊厥谱。Z-甘氨酸对士的宁敏感的甘氨酸受体以及与NMDA受体相关的士的宁不敏感的甘氨酸受体缺乏亲和力，这可能表明Z-甘氨酸要么通过前药机制起作用，要么本身通过另一种机制起作用。
