Imidazoleacetic acid
Imidazoleacetic acid is a naturally occurring endogenous metabolite of the neurotransmitter histamine. It might have a role as an endogenous signaling molecule or neurotransmitter. IAA is formed from histamine by the enzyme diamine oxidase.
Pharmacology
The compound is biologically active, acting as a relatively potent GABAA receptor partial agonist and GABAA-ρ receptor antagonist or weak partial agonist. It shows varying activational efficacies or functional selectivity at GABAA receptors of different α subunit compositions, with values ranging from 24 to 72%. Unlike certain other GABAA receptor agonists like muscimol, it is not a significant GABA reuptake inhibitor. In addition to its GABA receptor interactions, IAA is an imidazoline I1 receptor ligand. It has relatively low affinity for this receptor however and it is unknown whether it is an agonist or an antagonist. As a metabolite of histamine, it is structurally distinct from other GABAA receptor agonists. Unlike γ-aminobutyric acid, IAA is orally active and is readily able to cross the blood–brain barrier.IAA produces a hypnotic state resembling sleep when administered parenterally to animals. This is often or usually accompanied by seizures. Other effects include hyperactivity, ataxia, catalepsy, analgesia, hypothermia, and hypotension. Most of these effects are thought to be due to the compound's GABAA receptor interactions. The hypotensive effects of IAA might be mediated by imidazoline I1 receptor activation, although GABAA receptor activation could alternatively explain these particular effects.