Piperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909): high affinity ligands for the dopamine transporter.
A series of 4-[2-[bis(4-fluorophenyl)methoxy]ethylpiperidines were examined for their ability to bind to the dopamine transporter (DAT), the norepinephrine transporter, and the serotonin transporter (SERT). In particular, the role of the N-substituent on affinity and selectivity for the DAT was probed. 4-[2-[Bis(4-fluorophenyl)methoxy]ethyl-1-(2-naphthylmethyl)piperidine was found to possess subnanomolar affinity (K(i) = 0.7 nM) and good selectivity for the DAT (SERT/DAT = 323).
Prisinzano
Thomas
T
Laboratory of Medicinal Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Greiner
Elisabeth
E
Johnson
Edward M
EM
Dersch
Christina M
CM
Marcus
Jamila
J
Partilla
John S
JS
Rothman
Richard B
RB
Jacobson
Arthur E
AE
Rice
Kenner C
KC
D002352:Carrier Proteins / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D013329:Structure-Activity Relationship; D027981:Symporters / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D012701:Serotonin; C043425:vanoxerine; D004298:Dopamine; D009638:Norepinephrine