Imidazoleacetic acid
Pharmaceutical compound
From Wikipedia, the free encyclopedia
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]
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| 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 |
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| Formula | C5H6N2O2 |
| Molar mass | 126.115 g·mol−1 |
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Pharmacology
The compound is biologically active, acting as a relatively potent GABAA receptor partial agonist and GABAA-ρ receptor antagonist or weak partial agonist.[2][6] It shows varying activational efficacies or functional selectivity at GABAA receptors of different α subunit compositions, with Emax values ranging from 24 to 72%.[6][7] Unlike certain other GABAA 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 GABAA 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 GABAA receptor interactions.[2] The hypotensive effects of IAA might be mediated by imidazoline I1 receptor activation, although GABAA 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]