Aporphine enantiomers. Interactions with D-1 and D-2 dopamine receptors

Mol Pharmacol. 1984 Jan;25(1):18-23.

Abstract

The R(-) and the S(+) enantiomers of apomorphine (APO) and N-n-propyl norapomorphine (NPA) interact with both the D-1 and the D-2 dopamine receptors. R(-)-APO, as well as R(-)- and S(+)-NPA, stimulates the D-1 dopamine receptor in carp retina; S(+)-APO blocks this dopamine receptor. Similarly, R(-)-APO, as well as R(-)- and S(+)-NPA, stimulates the D-2 dopamine receptor in the intermediate lobe of the rat pituitary gland; S(+)-APO blocks the intermediate lobe D-2 receptor. The interactions between these aporphine enantiomers and the D-1 and the D-2 dopamine receptors exemplify several manifestations of the previously described "n-propyl phenomenon." Because S(+)-APO is distinguished from the other tested aporphines by its ability to antagonize either the D-1 or the D-2 dopamine receptors, it is hypothesized that the presence of an N-methylated tertiary amine in a molecule of appropriate configuration can confer dopamine receptor antagonist activity to the molecule.

Publication types

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

MeSH terms

  • Animals
  • Apomorphine / pharmacology*
  • Carps
  • Isomerism
  • Kinetics
  • Male
  • Pituitary Gland / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Retina / metabolism
  • Structure-Activity Relationship

Substances

  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Apomorphine