The psychopharmacology of isatin: a brief review

Abstract

Isatin is an endogenous indole with a distinct distribution in brain and tissues. In the brain its concentration is particularly high in hippocampus and cerebellum, at levels of about 0·1 μg/g. In vitro, it selectively inhibits monoamine oxidase (MAO) B; however, its most potent known action is as an inhibitor of atrial natriuretic peptide (ANP) receptors, preventing generation of the second messenger, cyclic GMP. In vivo, isatin induces an increase in monoamine levels in rat brain at doses ranging from 20 to 200 mg/kg. It is anxiogenic in a range of rodent and primate models at doses of 20 mg/kg; at doses greater than 50 mg/kg, it becomes sedative. It causes a rise in circulating cortisol in parallel with its anxiogenic effects. Brain levels of isatin are increased by the anxiogenic agent pentylene tetrazole. Isatin also appears to counteract the effects of ANP in vivo. It has been shown to reverse both the anxiolytic and memory-enhancing effects of ANP in rodent models, and also has an antidiuretic effect. At low doses, it inhibits food intake in mice. The only clinical study of isatin to date has been in bulimia nervosa, in which CSF levels were found to be raised. © 1998 John Wiley & Sons, Ltd.