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Neurochemicals for the Investigation of GABAC Receptors

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Abstract

GABAC receptors are being investigated for their role in many aspects of nervous system function including memory, myopia, pain and sleep. There is evidence for functional GABAC receptors in many tissues such as retina, hippocampus, spinal cord, superior colliculus, pituitary and the gut. This review describes a variety of neurochemicals that have been shown to be useful in distinguishing GABAC receptors from other receptors for the major inhibitory neurotransmitter GABA. Some selective agonists (including (+)-CAMP and 5-methyl-IAA), competitive antagonists (such as TPMPA, (±)-cis-3-ACPBPA and aza-THIP), positive (allopregnanolone) and negative modulators (epipregnanolone, loreclezole) are described. Neurochemicals that may assist in distinguishing between homomeric ρ1 and ρ2 GABAC receptors (2-methyl-TACA and cyclothiazide) are also covered. Given their less widespread distribution, lower abundance and relative structural simplicity compared to GABAA and GABAB receptors, GABAC receptors are attractive drug targets.

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Abbreviations

Aza-THIP:

4,5,6,7-tetrahydropyrazolo[3,4-c]pyridin-3-ol

CACA:

cis-4-aminocrotonic acid

(+)-CAMP:

(1S,2R)-2-aminomethylcyclopropanecarboxylic acid

(±)-cis-3-ACPBPA:

(±)-cis-(3-aminocyclopentanyl)butylphosphinic acid

5-Me-IAA:

5-methyl-1H-imidazole-4-acetic acid

2-Methyl-TACA:

trans-4-amino-2-methylbut-2-enoic acid

P4MPA:

(piperidin-4-yl)methylphosphinic acid

SGS742:

(3-aminopropyl)-n-butylphosphinic acid

THIP:

4,5,6,7-tetrahydroisolazolo[5,4-c]pyridin-3-ol

TPMPA:

(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid

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Authors and Affiliations

  1. Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology D06, The University of Sydney, Sydney, NSW, 2006, Australia

    Graham A. R. Johnston & Kenneth N. Mewett

  2. Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW, 2006, Australia

    Mary Chebib & Jane R. Hanrahan

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  1. Graham A. R. Johnston
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  2. Mary Chebib
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  4. Kenneth N. Mewett
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Correspondence to Graham A. R. Johnston.

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Special issue article in honour of Dr. Abel Lajtha.

The authors are pleased to honour Abel Lajtha for his expert stewardship of this journal since its inception and his generous assistance to many Australian neurochemists.

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Johnston, G.A.R., Chebib, M., Hanrahan, J.R. et al. Neurochemicals for the Investigation of GABAC Receptors. Neurochem Res 35, 1970–1977 (2010). https://doi.org/10.1007/s11064-010-0271-7

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