Discovery of non-zwitterionic GABA(A) receptor full agonists and a superagonist.
Numerous previous studies of GABA(A) receptor ligands have suggested that GABA(A) receptor agonists must be zwitterionic and feature an intercharge separation similar to that of GABA (approx. 4.7-6A). In this communication we demonstrate that appropriately functionalized GABA amides are partial, full, or superagonists, despite their non-zwitterionic structure.
Carlier
Paul R
PR
Department of Chemistry, Virginia Tech, Blacksburg 24061, USA. pcarlier@vt.edu
Chow
Ella S-H
ES
Barlow
Rebecca L
RL
Bloomquist
Jeffrey R
JR
D000577:Amides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002712:Chlorides / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000378:metabolism; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000577:Amides; D002712:Chlorides; D058785:GABA-A Receptor Agonists; D008024:Ligands; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid