title: Properties of 3-methyl-TIQ and 3-methyl-N-propargyl-TIQ for preventing MPTP-induced parkinsonism-like symptoms in mice.
abstract: BACKGROUND
  Selegiline, a therapeutic drug for Parkinson's disease (PD), structurally resembles the endogenous parkinsonism-related 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 disease-modifying therapy for PD, but also the N-propargyl functional group plays an important role in neuroprotection.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, 31-1 Tomitamachi, Koriyama, Fukushima 963-8611, Japan. k-abe@pha.ohu-u.ac.jp.
authors.forename: Kanako
authors.initials: K
authors.lastname: Saitoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
authors.forename: Terumasa
authors.initials: T
authors.lastname: Chiba
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katagiri
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saitoh
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Horiguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nojima
authors.forename: Kyoji
authors.initials: K
authors.lastname: Taguchi
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D018476:Hypokinesia / Q000378:metabolism / Q000517:prevention & control / Q000523:psychology; D020267:MPTP Poisoning / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: C534538:3-methyl-1,2,3,4-tetrahydroisoquinoline; C534539:3-methyl-N-propargyl-1,2,3,4-tetrahydroisoquinoline; D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine