The preparation of tritiated <i>E</i>‐ and <i>Z</i>‐4‐aminobut‐2‐enoic acids, conformationally restricted analogues of the inhibitory neurotransmitter 4‐aminobutanoic acid (GABA)

Duke, Rujee K.; Allan, Robin D.; Drew, Colleen A.; Johnston, Graham A.R.; Mewett, Kenneth N.; Long, Mervyn A.; Than, Chit

doi:10.1002/jlcr.2580330610

Cited by 10 publications

(3 citation statements)

References 30 publications

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“…Reduction of the triple bond in ATA and its derivatives with tritium has provided a convenient route to the preparation of GABA labelled to high specific activity due to the incorporation of four tritium atoms [17][18][19][20]. An improved synthesis of ATA has been reported [21].…”

Section: -Aminotetrolic Acidmentioning

confidence: 98%

“…It has been available commercially since 1992. Radioactive CACA has been prepared by reduction of an acetylenic intermediate with tritium gas [18]. The resultant high specific activity preparation of [ 3 H]CACA was found to be toxic producing burning sensations to the face, eyes and hands of personnel handling the preparation, thus limiting the extent of the binding studies that can be carried out.…”

Section: Cis-4-aminocrotonic Acidmentioning

confidence: 99%

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

Johnston

2015

Neurochem Res

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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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Section: -Aminotetrolic Acidmentioning

confidence: 98%

Section: Cis-4-aminocrotonic Acidmentioning

confidence: 99%

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

Johnston

2015

Neurochem Res

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“…Seasonal changes have been reported for inhibitory currents in rat hippocampus mediated via GABAA receptors (Edwards & Gage 1988). Preparation of [3H]-CACA has been done by tritiation of a derivative of 4-aminotetrolic acid (Duke et al 1993). Unfortunately, the toxic nature of the preparation has limited the extent of the binding studies that can be carried out thus far.…”

Section: Ligand Binding Studiesmentioning

confidence: 99%

Gaba Receptors: As Complex as Abc?

Johnston

1994

Clin Exp Pharma Physio

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1. Receptors for the inhibitory neurotransmitter GABA are currently classified pharmacologically into two major subtypes. 2. GABAA receptors are antagonized by the convulsant alkaloid bicuculline, and are insensitive to activation by the GABA analogue baclofen. GABAB receptors are insensitive to bicuculline and activated stereoselectively by baclofen. 3. There is increasing evidence for 'novel' GABA receptors that pharmacologically fall outside that defined by the GABAA/B classification. 4. GABA receptors insensitive to both baclofen and bicuculline have been described in the spinal cord, optic tectum, retina, cerebellum and hippocampus. In addition such novel GABA receptors may be widespread in insects and bacteria. These novel receptors have been given a variety of descriptions: GABAC, GABANANB (non-A, non-B) and GABA rho (cloned from retina). 5. cis-4-Aminocrotonic acid (CACA), a structural analogue of GABA in a folded conformation, is considered to be a selective agonist of the putative GABAC receptors. Tritiated CACA binds to cerebellar membranes in a GABA-sensitive, baclofen-insensitive manner. It can be displaced only by relatively high concentrations of bicuculline. 6. Autoradiographic studies show pronounced differences in regional distribution between the binding of CACA, the GABAA agonist muscimol and the GABAB agonist baclofen. 7. Novel GABA receptors may represent important new pharmacological targets.

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Syntheses and Uses of Isotopically Labelled Compounds ContainingCC,COorCNGroups

Zieliński

Kańska

2009

Patai's Chemistry of Functional Groups

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Introduction Syntheses and Uses of Compounds Containing C  C , C  O or C  N Groups Labelled with Stable Isotopes Synthesis and Uses of Compounds Containing C  C , C  O or CN Groups Labelled with Tritium Syntheses and Uses of Compounds Containing C  C , C  O or CN Groups Labelled with Radioactive Carbon Syntheses and Uses of Compounds Containing C  C , C  O or CN Groups Labelled with Radioactive Halogen Synthesis and Uses of Compounds Containing C  C , C  O , or CN Groups Labelled with Radioactive Sulphur Isotope Effect Studies Acknowledgements

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The preparation of tritiated E‐ and Z‐4‐aminobut‐2‐enoic acids, conformationally restricted analogues of the inhibitory neurotransmitter 4‐aminobutanoic acid (GABA)

Cited by 10 publications

References 30 publications

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

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

Gaba Receptors: As Complex as Abc?

Syntheses and Uses of Isotopically Labelled Compounds ContainingCC,COorCNGroups

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