Imidazoleacetic acid

Imidazoleacetic acid (also known as IAA, IMA, imidazole-4-acetic acid, or I4AA) is a naturally occurring endogenous metabolite of the neurotransmitter histamine (imidazole-4-ethylamine).^[2][3][4][5] It might have a role as an endogenous signaling molecule or neurotransmitter.^[6] IAA is formed from histamine by the enzyme diamine oxidase (DAO).^[3][2][4]

Imidazoleacetic acid

Clinical data
Other names	IAA; Imidazole-acetic acid; Imidazole-4-acetic acid; IMA; I4AA
Routes of administration	Oral[1]
Drug class	GABAA receptor partial agonist; GABAA-ρ receptor antagonist or weak partial agonist; Imidazoline I1 receptor ligand
ATC code	None
Identifiers
IUPAC name 2-(1H-imidazol-5-yl)acetic acid
CAS Number	645-65-8
PubChem CID	96215
ChemSpider	86856
UNII	IGZ30Z24EJ
KEGG	C02835
ChEBI	CHEBI:16974
ChEMBL	ChEMBL784
CompTox Dashboard (EPA)	DTXSID50214751
Chemical and physical data
Formula	C5H6N2O2
Molar mass	126.115 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=C(NC=N1)CC(=O)O
InChI InChI=1S/C5H6N2O2/c8-5(9)1-4-2-6-3-7-4/h2-3H,1H2,(H,6,7)(H,8,9) Key:PRJKNHOMHKJCEJ-UHFFFAOYSA-N

Pharmacology

The compound is biologically active, acting as a relatively potent GABA_A receptor partial agonist and GABA_A-ρ receptor antagonist or weak partial agonist.^[2][6] It shows varying activational efficacies or functional selectivity at GABA_A receptors of different α subunit compositions, with E_maxTooltip maximal efficacy values ranging from 24 to 72%.^[6][7] Unlike certain other GABA_A receptor agonists like muscimol, it is not a significant GABA reuptake inhibitor.^[5] In addition to its GABA receptor interactions, IAA is an imidazoline I₁ receptor ligand.^[2] It has relatively low affinity for this receptor however and it is unknown whether it is an agonist or an antagonist.^[2] As a metabolite of histamine, it is structurally distinct from other GABA_A receptor agonists.^[6] Unlike γ-aminobutyric acid (GABA), IAA is orally active and is readily able to cross the blood–brain barrier.^[2][6][5]

IAA produces a hypnotic state resembling sleep when administered parenterally to animals.^[2] This is often or usually accompanied by seizures.^[2] Other effects include hyperactivity, ataxia, catalepsy, analgesia, hypothermia, and hypotension.^[2] Most of these effects are thought to be due to the compound's GABA_A receptor interactions.^[2] The hypotensive effects of IAA might be mediated by imidazoline I₁ receptor activation, although GABA_A receptor activation could alternatively explain these particular effects.^[2]

Clinical studies

IAA has been clinically studied in humans, for instance in people with Huntington's disease.^[5][2][1] The drug was administered orally and intravenously, which appeared to successfully elevate circulating IAA concentrations.^[1] However, IAA did not produce behavioral or motor changes in the patients nor did it improve condition symptoms even when given at very high doses.^[5][2][1] It is possible that IAA may be rapidly eliminated in humans, which may limit the effects of exogenous IAA.^[5][1]

See also

• 1-Methylhistamine
• Piperidine-4-sulphonic acid
• Gaboxadol