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Unsaturated Analogues of the Neurotransmitter GABA: trans-4-Aminocrotonic, cis-4-Aminocrotonic and 4-Aminotetrolic Acids

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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.

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Acknowledgments

It is a pleasure to contribute to this special issue honouring Philip Beart who was my first PhD student. We have maintained our collaboration over many years most recently on aspects of the history of the International Society for Neurochemistry. I am grateful to Philip Beart, Jane Hanrahan and Ken Mewett for their helpful comments on the manuscript.

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  1. Pharmacology, Faculty of Medicine, School of Medical Sciences, The University of Sydney, Sydney, NSW, 2006, Australia

    Graham A. R. Johnston

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Correspondence to Graham A. R. Johnston.

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Special Issue: In Honor of Dr. Philip Beart.

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Johnston, G.A.R. Unsaturated Analogues of the Neurotransmitter GABA: trans-4-Aminocrotonic, cis-4-Aminocrotonic and 4-Aminotetrolic Acids. Neurochem Res 41, 476–480 (2016). https://doi.org/10.1007/s11064-015-1619-9

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  • DOI: https://doi.org/10.1007/s11064-015-1619-9

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