NEW PHENYLGLYCINE DERIVATIVES WITH POTENT AND SELECTIVE ANTAGONIST ACTIVITY AT PRESYNAPTIC GLUTAMATE RECEPTORS IN NEONATAL RAT SPINAL-CORD

被引:105
作者
JANE, DE [1 ]
PITTAWAY, K [1 ]
SUNTER, DC [1 ]
THOMAS, NK [1 ]
WATKINS, JC [1 ]
机构
[1] TOCRIS COOKSON,BRISTOL BS18 7DY,AVON,ENGLAND
基金
英国医学研究理事会;
关键词
ALPHA-METHYL-4-PHOSPHONOPHENYLGLYCINE (MPPG); ALPHA-METHYL-4-SULPHONOPHENYLGLYCINE (MSPG); ALPHA-METHYL-4-TETRAZOLYLPHENYLGLYCINE (MTPG); METABOTROPIC GLUTAMATE RECEPTOR (MGLUR) ANTAGONISTS; L-2-AMINO-4-PHOSPHONOBUTYRATE (L-AP4) RECEPTOR ANTAGONISTS; (1S,3S)-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID (ACPD) RECEPTOR ANTAGONISTS;
D O I
10.1016/0028-3908(95)00063-C
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The depression of the monosynaptic excitation of neonatal rat motoneurones produced by the metabotropic glutamate receptor (mGluR) agonists (1S,3S)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) or L-2-amino-4-phosphonobutyrate (L-AP4) was antagonized by three novel phenylglycine analogues: (RS)-alpha-methyl-4-sulphonophenylglycine (MSPG), (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) and (RS)-alpha-methyl-4-tetrazolylphenylglycin (MTPG). The potencies of all the new compounds were greater than that of the previously reported (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG). For L-AP4-sensitive presynaptic mGluRs, the order of antagonist potency found was MPPG > MSPG > MTPG > MCPG. In contrast, the order of antagonist potency found for (1S,3S)-ACPD-sensitive presynaptic mGluRs was MTPG > MPPG > MSPG > MCPG. To date, MPPG (K-D 9.2 mu M) is the most potent L-AP4-sensitive receptor antagonist yet tested on the neonatal rat spinal cord. In addition, MTPG (K-D 77 mu M) is the most potent antagonist yet tested for (1S,3S)-ACPD-sensitive receptors in this preparation.
引用
收藏
页码:851 / 856
页数:6
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