Synthesis and binding properties of [3H]NNC 12-0781, a new radioligand for the dopamine reuptake system.
The tritiated dopamine reuptake inhibitor [3H]NNC 12-0781 ([1-[2-(bis(4-fluorophenyl)-methoxy)-ethyl]-4-(3-(2-furanyl)-2,3-[3H] - propyl)-piperazine) was radiolabelled in one step starting from 1-[2-(bis(4-fluorophenyl)-methoxy)-ethyl]-4-(3-(2-furanyl)-2-propenyl)- piperazine, using tritium gas and PdO as catalyst. The radiochemical purity of [3H]NNC 12-0781 was higher than 99% after HPLC purification with a specific radioactivity of 21 Ci/mmol. [3H]NNC 12-0781 bound specifically to rat striatum in vitro at +4 degrees C with a Kd of 1.76 nM and Bmax of 587 fmol/mg tissue. The nonspecific binding was about 10% at Kd. At +37 degrees C no acceptable binding was observed. The association of [3H]NNC 12-0781 thus has the characteristics of a radioligand for the dopamine transporter in vitro at +4 degrees C.
Novo Nordisk A/S, Pharmaceuticals Division, Maaloev, Denmark.
L
L
Müller
H
H
Hall
C
C
Halldin
L
L
Farde
R
R
Hohlweg
P D
PD
Suzdak
E B
EB
Nielsen
C
C
Foged
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000138:chemical synthesis / Q000378:metabolism*; D007553:Isotope Labeling / Q000379:methods; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C097430:NNC 12-0781; D009419:Nerve Tissue Proteins; D010879:Piperazines; D014316:Tritium