Ibotenic acid

Ibotenic acid
Clinical data
Other names	Ibotenic acid; Ibotenate; Premuscimol
Routes of; administration	Oral
Drug class	NMDA receptor agonist; Metabotropic glutamate receptor agonist; GABAA receptor agonist; Neurotoxin; Hallucinogen
ATC code	None;
Identifiers
	IUPAC name (S)-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid;
CAS Number	2552-55-8 ;
PubChem CID	1233;
IUPHAR/BPS	1371;
ChemSpider	1196 ;
UNII	44AS82FRSI;
KEGG	C10600 ;
ChEBI	CHEBI:5854;
ChEMBL	ChEMBL284895 ;
CompTox Dashboard (EPA)	DTXSID40893771 ;
ECHA InfoCard	100.151.170
Chemical and physical data
Formula	C5H6N2O4
Molar mass	158.113 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	151 to 152 °C (304 to 306 °F) °C (anhydrous); 144-146 °C (monohydrate)
Solubility in water	H2O: 1 mg/mL; 0.1 M NaOH: 10.7 mg/mL; 0.1 M HCl: 4.7 mg/mL mg/mL (20 °C)
	SMILES O=C1/C=C(\ON1)C(C(=O)O)N;
	InChI InChI=1S/C5H6N2O4/c6-4(5(9)10)2-1-3(8)7-11-2/h1,4H,6H2,(H,7,8)(H,9,10) ; Key:IRJCBFDCFXCWGO-UHFFFAOYSA-N ;
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Ibotenic acid, or ibotenate, also known as premuscimol or as (S)-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, is a naturally occurring α-amino acid found in certain Amanita mushrooms such as Amanita muscaria. It acts primarily as a potent glutamate receptor agonist and produces neurological effects. The compound is used as a brain-lesioning agent in scientific research.

Ibotenic acid is a conformationally-restricted analogue of the excitatory neurotransmitter glutamate which acts as a non-selective agonist of glutamate receptors, strongly activating NMDA, group I and II metabotropic glutamate receptors, and weakly activating AMPA and kainate receptors. Taken systemically, it is a prodrug of muscimol, broken down by the liver into this more stable compound, which acts as a potent GABA_A and GABA_A-ρ receptor agonist. Although the compound's psychoactive effects are not well-understood, some researchers speculate that ibotenic acid itself may have stimulant-like properties. Ibotenic acid is biosynthesized from glutamic acid by hydroxylation catalyzed by an Fe(II)/2-oxoglutarate-dependent oxygenase, with subsequent conversion steps carried out by enzymes encoded within a linked biosynthetic gene cluster.

Ibotenic acid is commonly used in research to create site-specific hippocampal brain lesions in rats, allowing for task relearning due to its interaction with glutamate receptors, and is favored over other agents for its selectivity and long-term stability in saline solution. It induces excitotoxicity in rodents by overactivating NMDA and metabotropic glutamate receptors, leading to calcium overload and oxidative damage. In contrast, it targets glutamate-gated chloride channels in invertebrates, causing increased chloride permeability without affecting their excitatory glutamate receptors.