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| verifiedrevid = 445839922 |
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|ImageFile=Gabaculine.png |
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| verifiedrevid = 449582680 |
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| ImageFile=Gabaculine.svg |
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|IUPACName=(''RS'')-5-amino-1-cyclohexa-1,3-dienecarboxylic acid |
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| IUPACName= 5-Aminocyclohexa-1,3-diene-1-carboxylic acid |
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|Section1={{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CASNo=87980-11-8 |
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| CASNo=59556-29-5 |
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| PubChem=3445 |
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| PubChem = 3445 |
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| SMILES=C1C(C=CC=C1C(=O)O)N |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 3327 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 3F3ENU341O |
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| SMILES = O=C(O)\C1=C\C=C/C(N)C1 |
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| InChI = 1/C7H9NO2/c8-6-3-1-2-5(4-6)7(9)10/h1-3,6H,4,8H2,(H,9,10) |
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| InChIKey = KFNRJXCQEJIBER-UHFFFAOYAL |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C7H9NO2/c8-6-3-1-2-5(4-6)7(9)10/h1-3,6H,4,8H2,(H,9,10) |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = KFNRJXCQEJIBER-UHFFFAOYSA-N |
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|Section2={{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=7 | H=9 | N=1 | O=2 |
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| Formula=C<sub>7</sub>H<sub>9</sub>NO<sub>2</sub> |
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| MolarMass=139.15186 |
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|Section3={{Chembox Hazards |
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'''Gabaculine''' is a naturally occurring ] first isolated from the bacteria ''] toyacaensis'',<ref name="pmid862902">{{cite journal |author=Kobayashi K, Miyazawa S, Endo A |title=Isolation and inhibitory activity of gabaculine, a new potent inhibitor of gamma-aminobutyrate aminotransferase produced by a Streptomyces |journal=FEBS Letters |volume=76 |issue=2 |pages=207–10 |year=1977 |month=April |pmid=862902 |doi= 10.1016/0014-5793(77)80153-1|url=http://linkinghub.elsevier.com/retrieve/pii/0014-5793(77)80153-1 |issn=}}</ref> which acts as a potent and irreversible ] inhibitor,<ref name="pmid410442">{{cite journal |author=Rando RR |title=Mechanism of the irreversible inhibition of gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase by the neurotoxin gabaculine |journal=Biochemistry |volume=16 |issue=21 |pages=4604–10 |year=1977 |month=October |pmid=410442 |doi= 10.1021/bi00640a012|url= |issn=}}</ref><ref name="pmid18056209">{{cite journal |author=Irifune M, Katayama S, Takarada T, ''et al.'' |title=MK-801 enhances gabaculine-induced loss of the righting reflex in mice, but not immobility |journal=Can J Anaesth |volume=54 |issue=12 |pages=998–1005 |year=2007 |month=December |pmid=18056209 |doi= 10.1007/BF03016634|url=}}</ref> and also a ].<ref>Allan RD, Johnston GAR, Twitchin B. Effects of Gabaculine on uptake, binding and metabolism of GABA. ''Neuroscience Letters''. 1977;4:51-54.</ref><ref name="pmid17017962">{{cite journal |author=Høg S, Greenwood JR, Madsen KB, Larsson OM, Frølund B, Schousboe A, Krogsgaard-Larsen P, Clausen RP |title=Structure-activity relationships of selective GABA uptake inhibitors |journal=Current Topics in Medicinal Chemistry |volume=6 |issue=17 |pages=1861–82 |year=2006 |pmid=17017962 |doi= 10.2174/156802606778249801|url=http://www.bentham-direct.org/pages/content.php?CTMC/2006/00000006/00000017/0005R.SGM |issn=}}</ref> |
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'''Gabaculine''' is a naturally occurring ] first isolated from the bacteria ''] toyacaensis'',<ref name="pmid862902">{{cite journal |vauthors=Kobayashi K, Miyazawa S, Endo A |title=Isolation and inhibitory activity of gabaculine, a new potent inhibitor of gamma-aminobutyrate aminotransferase produced by a Streptomyces |journal=FEBS Letters |volume=76 |issue=2 |pages=207–10 |date=April 1977 |pmid=862902 |doi= 10.1016/0014-5793(77)80153-1|doi-access=free }}</ref> which acts as a potent and irreversible ] inhibitor,<ref name="pmid410442">{{cite journal |author=Rando RR |title=Mechanism of the irreversible inhibition of gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase by the neurotoxin gabaculine |journal=Biochemistry |volume=16 |issue=21 |pages=4604–10 |date=October 1977 |pmid=410442 |doi= 10.1021/bi00640a012}}</ref><ref name="pmid18056209">{{cite journal |vauthors=Irifune M, Katayama S, Takarada T, etal |title=MK-801 enhances gabaculine-induced loss of the righting reflex in mice, but not immobility |journal=Can J Anaesth |volume=54 |issue=12 |pages=998–1005 |date=December 2007 |pmid=18056209 |doi= 10.1007/BF03016634|doi-access=free }}</ref> and also a ].<ref>Allan RD, Johnston GAR, Twitchin B. Effects of Gabaculine on uptake, binding and metabolism of GABA. ''Neuroscience Letters''. 1977;4:51-54.</ref><ref name="pmid17017962">{{cite journal |vauthors=Høg S, Greenwood JR, Madsen KB, Larsson OM, Frølund B, Schousboe A, Krogsgaard-Larsen P, Clausen RP |title=Structure-activity relationships of selective GABA uptake inhibitors |journal=Current Topics in Medicinal Chemistry |volume=6 |issue=17 |pages=1861–82 |year=2006 |pmid=17017962 |doi=10.2174/156802606778249801 |url=http://www.bentham-direct.org/pages/content.php?CTMC/2006/00000006/00000017/0005R.SGM |archive-url=https://archive.today/20130414104450/http://www.bentham-direct.org/pages/content.php?CTMC/2006/00000006/00000017/0005R.SGM |url-status=usurped |archive-date=2013-04-14 }}</ref> Gabaculine is also known as 3-amino-2,3-dihydrobenzoic acid hydrochloride <ref name="MSDS">{{cite web|last1=Santa Cruz Biotechnology, Inc.|title=Gabaculine Material Safety Data Sheet|url=https://www.scbt.com/scbt/product/gabaculine-59556-17-1|access-date=5 December 2014}}</ref> and 5-amino cyclohexa-1,3 dienyl carboxylic acid.<ref name="Effects">{{cite journal|last1=Mutsui|first1=Yoshiki|last2=Deguchi|first2=Takehiko|title=Effects of gabaculine, a new potent inhibitor of gamma-aminobutyrate transaminase, on brain gamma-aminobutyrate content and convulsions in mice|journal=Life Sciences|date=1977|volume=20|issue=7|pages=1291–1296|doi=10.1016/0024-3205(77)90505-7|pmid=850479}}</ref> Gabaculine increased ] levels in the brain and had an effect on convulsivity in mice.<ref name="Effects" /> |
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== Mechanism of action == |
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Gabaculine includes a comparable structure to ] 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-prototrophic shift to the pyridoxamine imine.<ref name="Enzymatic book">{{cite book|last1=Frey|first1=Perry|last2=Ables|first2=Robert|last3=Hegeman|first3=Adrian|title=Enzymatic Reaction Mechanism|date=Dec 29, 2006|publisher=Oxford University Press Inc.|location=New York|isbn=0195122585|pages=262–263|url=https://books.google.com/books?id=6x3xHe2mG84C&pg=PA262 |access-date=4 December 2014}}</ref> Following this, a proton from the dihydrobenzene ring is abstracted by an enzymatic base, thus causing the ring to become aromatic.<ref name="Enzymatic book" /> The aromatic stabilization energy of the aromatic ring is what causes this reaction to be irreversible, thus causing the complex not to react further.<ref name="Enzymatic book" /> |
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==Preclinical studies== |
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Animal studies to determine the effect of gabaculine on GABA levels in the brain were heavily conducted around the 1970s.<ref name="In Vivo">{{cite journal|last1=Rando|first1=Robert|last2=Bangerter|first2=F.W.|title=The In Vivo Inhibition of GABA-transaminase by Gabaculine|journal=Biochemical and Biophysical Research Communications|date=May 13, 1977|volume=76|issue=4|pages=1276–1281|doi=10.1016/0006-291X(77)90993-7|pmid=901477}}</ref> 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.<ref name="Effects" /> |
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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.<ref name="Comparative">{{cite journal|last1=Loscher|first1=Wolfgang|title=A Comparative Study of the Pharmacology of lnhibitors of GABA-Metabolism|journal=Naunyn-Schmiedeberg's Arch. Pharmacol.|date=1980|volume=315|issue=2|pages=119–128|doi=10.1007/BF00499254|pmid=6782493|s2cid=26483388}}</ref> |
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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 ] of 35 mg/kg and {{LD50}} of 86 mg/kg.<ref name= "Comparative" /> Because of this potential lethal effect, gabaculine was proved to be too toxic for use as a drug however,<ref name="Enzymatic book" /> it can still be used as a compound to alter GABA levels in studies of experimental ].<ref name="Comparative" /> |
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==Regulation== |
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Gabaculine has not been approved by the FDA as a pharmaceutical entity; however, it can be used as a chemical compound for research purposes only.<ref>{{cite web|last1=PubChem|title=Gabaculine|url=https://pubchem.ncbi.nlm.nih.gov/compound/198382?from=summary#section=Top|website=pubchem.ncbi.nlm.nih.gov/|publisher=National Center for Biotechnology Information|access-date=9 December 2014}}</ref> This compound is not considered a hazardous substance according to OSHA 29 CFR 1910.1200.<ref name="MSDS" /> |
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==References== |
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==References== |
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{{reflist}} |
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{{GABA metabolism and transport modulators}} |
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{{GABAergics}} |
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