Properties of 3-methyl-TIQ and 3-methyl-Npropargyl- TIQ for preventing MPTP-induced parkinsonism-like symptoms in mice

Background: selegiline,a therapeutic drug for parkinson's disease (pd),structurally resembles the endogenous parkinsonismrelated compound 1,2,3,4-tetrahydroisoquinoline (tiq). in the present study,we evaluated the effects of 3-methyl-tiq (3-metiq) and 3-methyl-n-propargyl-tiq (3-me-n-protiq),selegiline mimetic tiq derivatives,for preventing 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (mptp)-induced parkinsonism-like symptoms in mice. methods:we evaluated the preventative effects of 3-metiq and 3-me-n-protiq on mptp-induced bradykinesia and depletion of striatal dopamine (da) and nigral tyrosine hydroxylase (th)-positive cells. results: mptp-induced bradykinesia was not different when mice were pretreated with 3-metiq,except for the high-dose group. however,pretreatment with 3-me-n-protiq significantly prevented the appearance of this akinesic status. mptp-induced striatal da and 3,4-dehydroxyphenylacetic acid reduction were significantly prevented by pretreatment with 3-me-n-protiq,but not 3-metiq,in a dose-dependent manner. on the other hand,levels of serotonin and its metabolite,5-hydroxyindole acetic acid,in the striatum were increased following treatment with 3-metiq. in addition,the mptp-induced decrease in th-positive cells in the substantia nigra was significantly reduced by pretreatment with 3-me-n-protiq,but not 3-metiq. conclusions: these results suggest that not only does 3-me-n-protiq have potential as a candidate compound for diseasemodifying therapy for pd,but also the n-propargyl functional group plays an important role in neuroprotection. copyright © 2013 by institute of pharmacology polish academy of sciences.