Article date: 1992/1/1
PubMed ID: 1319502
Journal name: Journal of neuroscience research (ISSN: 0360-4012)
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.
Author List: Aprison M H, Lipkowitz K B
Publication Types: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Isoxazoles; Receptors, GABA-A; Receptors, Glycine; Receptors, Neurotransmitter; Muscimol; gamma-Aminobutyric Acid; N,N-dimethylmuscimol; N-methylmuscimol; 6-methyl-4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol; N,N-dimethylthiomuscimol; gaboxadol; Glycine;
Mesh terms: Chemical Phenomena; Chemistry, Physical; Computer Simulation; Glycine/antagonists & inhibitors; Isoxazoles/chemistry; Models, Molecular; Molecular Structure; Muscimol/analogs & derivatives; Receptors, GABA-A/drug effects; Receptors, Glycine; Receptors, Neurotransmitter/drug effects; Structure-Activity Relationship; gamma-Aminobutyric Acid/chemistry;