Structural factors governing agonist and antagonist activity in the GABAA system.
By comparing the structures of GABA and semi-rigid GABAA analogues, a distinction between structural requirements for agonist and antagonist activity at the GABAA receptor has been suggested, based on differences in arrangements of charge centres. However, additional structural distinction(s) appear to be necessary since the GABA molecule itself can attain the arrangements suggested for both agonist and antagonist activity, and GABA is not an antagonist. We now propose that a specifically located benzene ring and steric effects in the N+ region are also involved in distinguishing between GABAA-active compounds.
Pooler
G W
GW
Molecular Medicine Group, City University, London, U.K.
Steward
E G
EG
D001640:Bicuculline / Q000378:metabolism; D007555:Isoxazoles / Q000378:metabolism; D008958:Models, Molecular; D011963:Receptors, GABA-A / Q000378:metabolism; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000378:metabolism*
D007555:Isoxazoles; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C015542:gaboxadol; D001640:Bicuculline