SULFHYDRYL DRUGS REDUCE NEUROTOXICITY OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) IN THE MOUSE

Striatal levels of dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased 7 days after subcutaneous injection of MPTP (20mg/kg) to the mouse. Striatal GSH contents decreased and GSSG/GSH ratios increased one hour after subcutaneous administration of MPTP. Pretreatments of both cysteamine (200 mg/kg, s. c.) and dimercaprol (20 mg/kg, i. m.) reduced the MPTP-induced decreases in striatal dopamine, DOPAC and HVA, and also prevented the MPTP-induced decreases in GSH levels and increases in GSSG/GSH ratios. On the other hand, injection of cysteamine did not modify the MPTP-induced decreases in striatal levels of dopamine and its metabolites when it was done 2 hours after MPTP administration. Moreover, pretreatment of cysteamine did not affect striatal concentrations of MPP+ in MPTP-treated mice. These results suggest that sulfhydryl drugs such as cysteamine and dimercaprol may reduce neurotoxicity of MPTP probably via changes in redox cycle of glutathione in the brain.