Ibotenic acid

Source: Wikipedia, the free encyclopedia.

Not to be confused with Ibogaine, a different psychoactive compound.
Ibotenic acid
Names
IUPAC name
(S)-2-Amino-2-(3-hydroxyisoxazol-5-yl)acetic acid
Other names
Ibotenic acid
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard
 100.151.170 Edit this at Wikidata
EC Number
  • 622-405-7
IUPHAR/BPS
KEGG
UNII
  • InChI=1S/C5H6N2O4/c6-4(5(9)10)2-1-3(8)7-11-2/h1,4H,6H2,(H,7,8)(H,9,10) checkY
    Key: IRJCBFDCFXCWGO-UHFFFAOYSA-N checkY
  • InChI=1/C5H6N2O4/c6-4(5(9)10)2-1-3(8)7-11-2/h1,4H,6H2,(H,7,8)(H,9,10)
    Key: IRJCBFDCFXCWGO-UHFFFAOYAQ
  • (S)-: Key: IRJCBFDCFXCWGO-BYPYZUCNSA-N
SMILES
  • O=C1/C=C(\ON1)C(C(=O)O)N
Properties
C5H6N2O4
Molar mass 158.113 g·mol−1
Melting point 151-152 °C (anhydrous)
144-146 °C (monohydrate)
H2O: 1 mg/mL
0.1 M NaOH: 10.7 mg/mL
0.1 M HCl: 4.7 mg/mL
Hazards
GHS labelling:[1]
GHS06: Toxic
Danger
H301
P264, P270, P301+P316, P321, P330, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Ibotenic acid or (S)-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a

better source needed
]

Pharmacology

Amanita muscaria, which contains ibotenic acid

Ibotenic acid acts as a potent

mGluR3) metabotropic glutamate receptors.[3][7] It is inactive at group III mGluRs.[8] Ibotenic acid also acts as a weak agonist of the AMPA and kainate receptors.[3][7] In addition, due to in vivo decarboxylation into muscimol, it acts indirectly as a potent GABAA and GABAA-ρ receptor agonist.[7] Unlike muscimol—the principal psychoactive constituent of Amanita muscaria that is understood to cause sedation and delirium—ibotenic acid's psychoactive effects are not known independent of its serving as a prodrug to muscimol, although some researchers have speculated that it would act as a stimulant.[9][10]

Biological properties

Mechanism of action

Ibotenic acid is an

NMDA, and trans-ACPD receptor sites in multiple systems in the central nervous system. Ibotenic neurotoxicity can be enhanced by glycine and blocked by dizocilpine. Dizocilpine acts as an uncompetitive antagonist at NMDA receptors.[11]

Ibotenic acid toxicity comes from activation of the

long term potentiation
or LTP. The process of long term potentiation is believed to be related to the acquisition of information. The NMDA receptor functions properly by allowing Ca2+ ions to pass through after activation at the receptor site.

Activated NMDAR

The binding of ibotenic acid allows excess Ca2+ into the system which results in neuronal cell death. Ca2+ also activates

CaM-KII or Ca2+/Calmodulin Kinase which phosphorylates multiple enzymes. The activated enzymes then begin producing reactive oxygen species which damages surrounding tissue. The excess Ca2+ results in the enhancement of the mitochondrial electron transport system which will further increase the number of reactive oxygen species.[12]

Biological effects

Ibotenic acid typically affects both NMDA and

APCD or metabolotropic quisqualate receptor sites in the central nervous system.[11]
Due to their targeting of these systems the symptoms associated with Ibotenic acid poisoning are often related to perception and control.

At least some ingested ibotenic acid is likely

auditory distortions, sensations of floating, and retrograde amnesia.[14]

Symptoms are slightly different for children, typically beginning after 30–180 minutes. Dominant symptoms in children include ataxia, obtundation, and lethargy. Seizures are occasionally reported, however, more commonly with children.[14]

Treatment

Treatment of ibotenic acid toxicity centres around supportive care and treatment of symptoms; no antidote is available. Gastric decontamination with

activated charcoal or gastric lavage can be of benefit if the patient presents early. The psychotropic effects and hallucinations ibotenic acid and its metabolite muscimol produce are best managed in a quiet environment with minimal stimulation. Benzodiazepines can be of benefit in agitated or panicked patients; they can also be used to control seizures if they occur. Benzodiazepines as a GABA-A PAM interacts with Muscimol as a GABA-A agonist and may cause a significantly increased risk of depressant effects. Airway management may be required if sedation is profound. Symptoms usually resolve within a few hours of ingestion but can last for days following significant exposures.[15]

Monitoring for the presence of brain lesions may be required following a large or repeated exposure. Other measures may be required if the patient has been exposed to a mushroom such as Amanita muscaria as other active compounds may be present.[16]

Use in research

Ibotenic acid used for the lesioning of rat's brains is kept frozen in a phosphate-buffered

perforant pathway
.

Typically, when lesioning is done with other chemicals the subject cannot relearn a task. However, due to Ibotenic acid's reactivity with glutamate receptors such as the NMDA receptor, Ibotenic acid lesioning does allow the subject to relearn tasks. Ibotenic acid lesioning is thus preferred in studies where re-learning a task after lesioning is essential. Compared to other lesioning agents, Ibotenic acid is one of the most site-specific; however, less-damaging alternatives are presently sought.[17]

Biosynthesis

Ibotenic acid's biosynthetic genes are organized in a physically linked biosynthetic gene cluster. The biosynthetic pathway is initiated by hydroxylation of glutamic acid by a dedicated Fe(II)/2-oxoglutarate-dependent oxygenase. The reaction yields threo-3-hydroxyglutamic acid, which is converted into ibotenic acid, likely by enzymes encoded in the biosynthetic gene cluster.[18]

See also

References

  1. ^ "Ibotenic acid". pubchem.ncbi.nlm.nih.gov.
  2. S2CID 44494685
    .
  3. ^
    ISBN 978-0-415-28288-8
    .
  4. S2CID 25172395
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  5. S2CID 4342937
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  6. S2CID 91380050
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  7. ^
    ISBN 978-90-5702-054-4
    .
  8. PMID 14985045
    .
  9. ^ Chilton 1975; Theobald et al. 1968
  10. ^ Chilton 1975; Ott 1976a
  11. ^
    PMID 1325800
    .
  12. ^ Sureda, F. "Excitotoxicity and the NMDA receptor". eurosiva. Retrieved 30 April 2015.
  13. PMID 12747324
    .
  14. ^ a b Duffy, Thomas. "Symptoms of ibotenic/muscimol poisoning (isoxazol poisoning)". Toxic Fungi of Western North America. MykoWeb. Retrieved 30 April 2015.
  15. ^ Rolston-Cregler, Louis. "Hallucinogenic Mushroom Toxicity". MedScape. Retrieved 30 April 2015.
  16. PMID 12747324
    .
  17. S2CID 3767525
    .
  18. PMID 32233056
    .
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