Isatin: role in stress and anxiety.

(Indoledione 2,3) isatin is an endogenous indole found both in mammalian brain and peripheral tissues. Isatin concentration in blood can exceed 1 microM and tissue concentrations vary from < 0.1 to 10 microM. Its level in the brain and periphery is increased by stress. Isatin has a wide spectrum of behavioural and metabolic effects. It is anxiogenic at lower doses and sedative at higher doses. Its most potent known in vitro actions are as an antagonist of atrial natriuretic peptide (ANP) function and NO signaling. In this review, we discuss isatin and stress in animal models, the few human studies, and also what it is known to date about the molecular mechanisms of its action. We suggest the possibility that isatin and its analogues may be interesting new pharmacological agents; Isatin antagonists may be anxiolytic, and isatin agonists may activate the HPA axis.