Effect of tetrabenazine on the striatal uptake of exogenous L-DOPA in vivo: a PET study in young and aged rhesus monkeys.
The effect of tetrabenazine (TBZ) pretreatment on the striatal uptake of exogenous L-DOPA in vivo was assessed noninvasively in rhesus monkeys by positron emission tomography (PET) using the tracer [(18)F]-FluoroDOPA (FDOPA). Paired studies were done comparing baseline vs. TBZ treatment on the uptake of FDOPA, a measure of aromatic L-amino acid decarboxylase (AAAD) activity. Results show increased AAAD activity with TBZ treatment. These results suggest that the action of TBZ as a dopamine antagonist dominates more than its expected action as a potent vesicular monoamine transporter (VMAT2) inhibitor. Results also showed diminished responsivity of AAAD to TBZ challenge in aged monkey brain.
DeJesus
Onofre T
OT
Medical Physics Department, University of Wisconsin Medical School, 1530 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706, USA. odejesus@facstaff.wisc.edu
Shelton
Steven E
SE
Roberts
Andrew D
AD
Nickles
Robert J
RJ
Holden
James E
JE
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D015259:Dopamine Agents / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D007980:Levodopa / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides; D013747:Tetrabenazine / Q000494:pharmacology*; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D018759:Adrenergic Uptake Inhibitors; D015259:Dopamine Agents; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C043437:fluorodopa F 18; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D013747:Tetrabenazine