title: Unsaturated Analogues of the Neurotransmitter GABA: trans-4-Aminocrotonic, cis-4-Aminocrotonic and 4-Aminotetrolic Acids.
abstract: Analogues of the neurotransmitter GABA containing unsaturated bonds are restricted in the conformations they can attain. This review traces three such analogues from their synthesis to their use as neurochemicals. trans-4-Aminocrotonic acid was the first conformationally restricted analogue to be extensively studied. It acts like GABA across a range of macromolecules from receptors to transporters. It acts similarly to GABA on ionotropic receptors. cis-4-Aminocrotonic acid selectively activates bicuculline-insensitive GABAC receptors. 4-Aminotetrolic acid, containing a triple bond, activates bicuculline-sensitive GABAA receptors. These findings indicate that GABA activates GABAA receptors in extended conformations and GABAC receptors in folded conformations. These and related analogues are important for the molecular modelling of ionotropic GABA receptors and to the development of new agents acting selectively on these receptors.
authors.affiliation: Pharmacology, Faculty of Medicine, School of Medical Sciences, The University of Sydney, Sydney, NSW, 2006, Australia. grahamj@mail.usyd.edu.au.
authors.forename: Graham A R
authors.initials: GA
authors.lastname: Johnston
mesh_terms: D000613:Aminobutyrates / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D003437:Crotonates / Q000737:chemistry* / Q000494:pharmacology*; D018755:GABA Agonists / Q000737:chemistry / Q000494:pharmacology; D018756:GABA Antagonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000494:pharmacology; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000613:Aminobutyrates; D003437:Crotonates; D018755:GABA Agonists; D018756:GABA Antagonists; C087200:GABA-C receptor; D018377:Neurotransmitter Agents; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C055331:4-aminocrotonic acid; C000148:4-aminotetrolic acid; D005680:gamma-Aminobutyric Acid
keywords: 4-Aminotetrolic acid; GABA; GABAA receptors; GABAC receptors; cis-4-Aminocrotonic acid; trans-4-Aminocrotonic acid