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.