No reduction of dopamine transporter binding sites in mice following treatment with the TIQ analogue 1-benzyl-1,2,3,4-tetrahydroisoquinoline.
1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) and TIQ are endogenous substances inducing bradykinesia, one of the symptoms of parkinsonism, in rodents and primates, and 2-methyl-TIQ is postulated to be an active form of TIQ. We investigated the effect of 1-BnTIQ-, TIQ- or 2-methyl-TIQ-treatment on the binding of 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-[N-methyl-11C]tropane to striatal dopamine transporters (DATs) in mice. Neither 1-BnTIQ (80 mg/kg, i.p., twice per day for 10 days) nor 2-methyl-TIQ (40 mg/kg, i.p., twice per day for 10 days) affected the radioligand-DAT binding, while TIQ (80 mg/kg, i.p., twice per day for 10 days) induced a 14% decrease. These results indicate that 1-BnTIQ does not affect the density of DATs on dopaminergic neurons, and that it is not clear whether or not 2-methyl-TIQ is an active form of TIQ.
Ishiwata
Kiichi
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi, Tokyo 173-0022, Japan. ishiwata@pet.tmig.or.jp
Koyanagi
Yasuhiro
Y
Abe
Kenji
K
Kawamura
Kazunori
K
Taguchi
Kyoji
K
Saitoh
Toshiaki
T
Toda
Jun
J
Sano
Takehiro
T
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D044005:Tetrahydroisoquinolines
D050483:Dopamine Plasma Membrane Transport Proteins; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493215:Slc6a3 protein, mouse; D044005:Tetrahydroisoquinolines; C084924:1,2,3,4-tetrahydro-1-(phenylmethyl)isoquinoline