Piperidine analogues of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909): high affinity ligands for the dopamine transporter

J Med Chem. 2002 Sep 12;45(19):4371-4. doi: 10.1021/jm020264r.

Abstract

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).

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / metabolism
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins*
  • Norepinephrine / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Radioligand Assay
  • Serotonin / metabolism
  • Serotonin Plasma Membrane Transport Proteins
  • Structure-Activity Relationship
  • Symporters / metabolism

Substances

  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Norepinephrine Plasma Membrane Transport Proteins
  • Piperazines
  • Serotonin Plasma Membrane Transport Proteins
  • Symporters
  • Serotonin
  • vanoxerine
  • Dopamine
  • Norepinephrine