Isatin (Indoline-2,3-dione) is a potent inhibitor of monoamine oxidase (MAO) with an IC50 of 3 μM, also binds to central benzodiazepine receptors (IC50 against clonazepam, 123 μM)[3]. Isatin is an endogenous indole that is increased in stress, inhibits monoamine oxidase (MAO) B and improves bradykinesia and striatal dopamine levels in rat models of Parkinson's disease. In dopaminergic SH-SY5Y cells (human neuroblastoma) isatin (1-400 μM) induces cell death in dose- and time dependent manner. This death occurred as a continuum of survival, apoptosis and necrosis[4]. A single dose of isatin (80 mg/kg) has a rapid effect on the serotonergic system in the hypothalamus. Isatin significantly increases 5-HT concentrations in the hypothalamus and cortex but did not significantly alter 5-HIAA concentrations[5]. Isatin concentration in blood can exceed 1 mM and tissue concentrations vary from < 0.1 to 10 mM. 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[6]. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration[7].
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