MUSCIMOL AND N,N-DIMETHYLMUSCIMOL - FROM A GABA AGONIST TO A GLYCINE ANTAGONIST

被引:8
作者
APRISON, MH
LIPKOWITZ, KB
机构
[1] INDIANA UNIV,SCH MED,INST PSYCHIAT RES,APPL & THERET NEUROBIOL,INDIANAPOLIS,IN 46202
[2] INDIANA UNIV,DEPT PSYCHIAT,INST PSYCHIAT RES,INDIANAPOLIS,IN 46202
[3] INDIANA UNIV,DEPT BIOCHEM,INDIANAPOLIS,IN 46202
[4] INDIANA UNIV PURDUE UNIV,DEPT CHEM,INDIANAPOLIS,IN 46202
关键词
MOLECULAR MODELING; PHYSIOLOGICAL FUNCTION; GABANERGIC RECEPTORS;
D O I
10.1002/jnr.490310122
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
By using molecular modeling methods, a molecular mechanism was identified which can explain how the incorporation of two methyl groups in place of two hydrogen atoms on the terminal nitrogen atom of muscimol can not only convert this potent agonist at GABAnergic receptors to an inactive molecule at these receptors, but also can convert this new derivative to an antagonist of glycine at glycinergic receptors. This insight into the molecular mechanism operative in the conversion of physiological function provides a basis for understanding how a single molecule may be able to act at both the GABA- and glycine-inhibitory receptors.
引用
收藏
页码:166 / 174
页数:9
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