Isatin

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Background

IC50: 15 μMIsatin is a monoamine oxidase inhibitor.Monoamine oxidase inhibitors have been used as therapies for the treatment of depression, particularly in treating atypical depression. Monoamine oxidase inhibitors are also used in the treatment of Parkinson's disease and other disorders.In vitro: Previous study found that isatin treatment at 1-400 μM for 24h could induce a significant dose-dependent increase in MTT metabolism by SH-SY5Y cells, which was not due to the increase in cell division. In addition, isatin at the higher concentrations was able to trigger cell death, though MTT metabolism was still increased, indicating that the surviving cells were hypermetabolic. With a longer treatment, isatin was found to cause cell death in a dose-dependent manner, and the predominant mode of cell death was apoptosis at lower concentrations, while at the highest concentration increasing numbers of necrotic cells were also observed [1]. In vivo: Animal study showed that the motor activity of Japanese encephalitis virus (JEV)-induced rats receiving isatin was improved significantly when compared with that of untreated JEV-infected rats. In addition, isatin was able to prevent the decrease in striatal DA levels in JEV-rats and the increased turnover of dopamine (DA) (DOPAC/DA) induced by JEV was significantly inhibited by isatin. Such results indicated that the exogenously administered isatin was able to improve JEV-induced parkinsonism via increasing the striatum DA concentrations [2]. Clinical trial: Up to now, isatin is still in the preclinical development stage.

[1] Igosheva N,Lorz C,O'Conner E,Glover V,Mehmet H. Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells. Neurochem Int.2005 Aug;47(3):216-24.
[2] Hamaue N,Minami M,Terado M,Hirafuji M,Endo T,Machida M,Hiroshige T,Ogata A,Tashiro K,Saito H,Parvez SH. Comparative study of the effects of isatin, an endogenous MAO-inhibitor, and selegiline on bradykinesia and dopamine levels in a rat model of Parkinson's disease induced by the Japanese encephalitis virus. Neurotoxicology.2004 Jan;25(1-2):205-13.