Isatin is an endogenous indole with a distinctive distribution in brai
n and tissues. In the brain, the highest levels have been found in the
hippocampus (0.1 mu g/g), and an immunocytochcmical stain has shown s
pecific localization within particular cells. In vitro, its most poten
t known actions are as an inhibitor of monoamine oxidase B (IC50 simil
ar to 3 mu M), and of atrial natriuretic peptide (ANP) receptor bindin
g and ANP-induced guanylate cyclase (both with an IC50 similar to 0.4
mu M). In vivo, isatin administration (10-200 mg/kg) causes an increas
e of monoamine neurotransmitter levels in the brain. Isatin is anxioge
nic in animal models at doses of 10-20 mg/kg and sedative at higher do
ses. Its anxiogenic effects are unlikely to be due to inhibition of mo
noamine oxidase, but may possibly stern from interaction with the ANP
system. Isatin may mediate a link between monoamines and the natriuret
ic peptide system, and its analogues may provide new pharmacological t
ools.