Gabaculine

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Gabaculine
Gabaculine.png
Names
IUPAC name
5-aminocyclohexa-1,3-diene-1-carboxylic acid
Identifiers
59556-17-1 N
ChemSpider 3327 N
Jmol 3D model Interactive image
PubChem 3445
  • InChI=1S/C7H9NO2/c8-6-3-1-2-5(4-6)7(9)10/h1-3,6H,4,8H2,(H,9,10) N
    Key: KFNRJXCQEJIBER-UHFFFAOYSA-N N
  • InChI=1/C7H9NO2/c8-6-3-1-2-5(4-6)7(9)10/h1-3,6H,4,8H2,(H,9,10)
    Key: KFNRJXCQEJIBER-UHFFFAOYAL
  • O=C(O)\C1=C\C=C/C(N)C1
Properties
C7H9NO2
Molar mass 139.15186
Vapor pressure {{{value}}}
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Gabaculine is a naturally occurring neurotoxin first isolated from the bacteria Streptomyces toyacaensis,[1] which acts as a potent and irreversible GABA transaminase inhibitor,[2][3] and also a GABA reuptake inhibitor.[4][5] Gabaculine is also known as 3-amino-2,3-dihydrobenzoic acid hydrochloride [6] and 5-amino cyclohexa-1,3 dienyl carboxylic acid.[7] Gabaculine increased GABA levels in the brain and had an effect on convulsivity in mice.[7]

Mechanism of Action

Gabaculine includes a comparable structure to GABA and a dihydrobenzene ring. This comparable GABA structure is used in order to be able to take the place of GABA during the first steps of transamination, including transaldimination and 1,3-prototrphic shift to the pyridoxamine imine.[8] Following this, a proton from the dihydrobenzene ring is abstracted by an enzymatic base, thus causing the ring to become aromatic.[8] The aromatic stabilization energy of the aromatic ring is what causes this reaction to be irreversible, thus causing the complex not to react further.[8]

Pre-Clinical Studies

Animal studies to determine the effect of gabaculine on GABA levels in the brain were heavily conducted around the 1970s.[9] These in vivo studies involved mostly the use of mice that underwent intravenous administration of this drug. Each of these studies concluded that gabaculine has a great potential to increase the GABA levels in the brain of these mice in a time dependent manner.[7] Along with determining the effect of GABA levels, in vivo studies were conducted to investigate the ability of gabaculine to inhibit convulsions in mice. Results indicated that gabaculine provided a clear anticonvulsant effect against seizures induced by high doses of chemoconvulsants or electroshock.[10] The toxicity of this compound was also investigated using animal mouse models. This study showed that at anticonvulsant doses, gabaculine is extremely potent and toxic when compared to other GABA transaminase inhibitors, with an ED50 of 35 mg/kg and LD50 of 86 mg/kg.[10] Because of this potential lethal effect, gabaculine was proved to be too toxic for use as a drug however,[8] it can still be used as a compound to alter GABA levels in studies of experimental epilepsy.[10]

Chemical Product and Regulation

Gabaculine has not been found to be approved by the FDA as a pharmaceutical entity; however, it can be used as a chemical compound for research purposes only.[11] This product can be purchased with the intent of research use from most chemical companies. Gabaculine was discontinued from Sigma Aldrich; however a 250 mg pack size can still be purchased while inventory is still in stock.[12] This compound is part of Sigma Aldrich's Library of Pharmacologically Active Compounds (LOPAC), a library of high quality, ready to screen compounds.[12] Finetech Industry Limited, Angene Chemical, and MP Biomedicals are available for the purchase of this compound as well.[13] A gabaculine material safety and data sheet from Santa Cruz Biotechnology indicates that this compound is not considered a hazardous substance according to OSHA 29 CFR 1910.1200.[6] Also based on this material safety and data sheet that this compound is found on the following regulatory lists:US-California Permissible Exposure Limits for Chemical Contaminants","US - Hawaii Air Contaminant Limits","US - Massachusetts Drinking Water – Secondary Contaminants Maximum Contaminant Levels (MCLs)","US - Michigan Exposure Limits for Air Contaminants","US - Oregon Permissible Exposure Limits (Z-1)","US - Oregon Permissible Exposure Limits (Z-3)","US - Tennessee Occupational Exposure Limits - Limits For Air Contaminants","US - Utah Secondary Drinking Water Standards - Inorganic Contaminants","US - Wyoming Toxic and Hazardous Substances Table Z1 Limits for Air Contaminants","US Clean Air Act (CAA) National Ambient Air Quality Standards (NAAQS)","US OSHA Permissible Exposure Levels (PELs) - Table Z3","WHO Guidelines for Drinking-water Quality - Chemicals for which guideline values have not been established".[6]

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Allan RD, Johnston GAR, Twitchin B. Effects of Gabaculine on uptake, binding and metabolism of GABA. Neuroscience Letters. 1977;4:51-54.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 6.2 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ 7.0 7.1 7.2 Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ 8.0 8.1 8.2 8.3 Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ 10.0 10.1 10.2 Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ 12.0 12.1 Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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