Pharmacology and function of imidazole 4-acetic acid in brain.

1. Imidazole 4-acetic acid (IMA) is a naturally occurring metabolite in brain, although it is unclear what biochemical pathways are involved in its biosynthesis and breakdown. Some evidence, however, suggests that IMA is an oxidation product of histamine. 2. The compound has pronounced neuropharmacological properties, many of which are consistent with an activation of GABA(A) receptors. Indeed, IMA is able to displace [3H]GABA from GABA(A) sites in a potent manner. 3. IMA displays definite partial agonist characteristics as an enhancer of benzodiazepine binding to the GABA(A) receptor complex in membrane preparations. In addition, it has an affinity for GABA(C) receptors, where it seems to act as an antagonist, and perhaps as a weak partial agonist. A third recognition site for IMA in brain is the I1-imidazoline receptor. 4. Parenteral administration to experimental animals leads to a sleep-like state which can often be accompanied by seizures. In addition, central application of IMA has been associated with a dose-related reduction in arterial pressure and sympathetic nervous discharge. 5. No specific receptor site or uptake system for IMA has yet been discovered, adding uncertainty to its role in central nervous system function. Yet the possibility cannot be overlooked that IMA plays a role in regulating blood pressure.