PHARMACOLOGY AND FUNCTION OF IMIDAZOLE 4-ACETIC ACID IN BRAIN

1. Imidazole 4-acetic acid (IMA) is a naturally occurring metabolite i n brain, although it is unclear what biochemical pathways are involved in its biosynthesis and breakdown. Some evidence, however, suggests t hat IMA is an oxidation product of histamine. 2. The compound has pron ounced neuropharmacological properties, many of which are consistent w ith an activation of GABAA receptors. Indeed, IMA is able to displace [H-3]GABA from GABAA sites in a potent manner. 3. IMA displays definit e partial agonist characteristics as an enhancer of benzodiazepine bin ding to the GABAA receptor complex in membrane preparations. In additi on, it has an affinity for GABAc receptors, where it seems to act as a n antagonist, and perhaps as a weak partial agonist. A third recogniti on site for IMA in brain is the I-1-imidazoline receptor. 4. Parentera l administration to experimental animals leads to a sleep-like state w hich can often be accompanied by seizures. In addition, central applic ation of IMA has been associated with a dose related reduction in arte rial pressure and sympathetic nervous discharge. 5. No specific recept or site or uptake system for IMA has yet been discovered, adding uncer tainty to its role in central nervous system function. Yet the possibi lity cannot be overlooked that IMA plays a role in regulating blood pr essure. (C) 1998 Elsevier Science Inc.