R(-)2-fluoro-N-n-propylnorapomorphine: a very potent and D2-selective dopamine agonist

Neuropharmacology. 1991 Jan;30(1):97-9. doi: 10.1016/0028-3908(91)90049-h.

Abstract

A series of 2-substituted N-n-propylnorapomorphine (NPA) derivatives were synthesized and compared with other DA agonists for affinity to D1 and D2 dopamine (DA) receptors in rat brain corpus striatum tissue. The 2-substituents tested reduced D1 affinity similarly, but enhanced D2 affinity in the rank order: F greater than OH greater than Br greater than OCH3 greater than H greater than or equal to NH2. The extraordinarily high D2 affinity (Ki = 12 pM) and D2 vs. D1 selectivity (57,500) of 2-F-NPA far-exceeded that of all other DA agonists tested, and it was about 10-times more potent than NPA in vivo.

Publication types

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

MeSH terms

  • Animals
  • Apomorphine / analogs & derivatives*
  • Apomorphine / metabolism
  • Apomorphine / pharmacology
  • Cell Membrane / metabolism
  • Corpus Striatum / metabolism*
  • Dopamine Agents / pharmacology*
  • Kinetics
  • Male
  • Rats
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Structure-Activity Relationship

Substances

  • Dopamine Agents
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • 2-fluoro-N-n-propylnorapomorphine
  • Apomorphine