Synthesis and dopamine agonist and antagonist effects of (R)-(-)- and (S)-(+)-11-hydroxy-N-n-propylnoraporphine

J Med Chem. 1988 Jul;31(7):1392-6. doi: 10.1021/jm00402a024.

Abstract

The R-(-) and S-(+) enantiomers of 11-hydroxy-N-n-propylnoraporphine, (R)-3 and (S)-3, were synthesized in six steps from 1-(3-methoxy-2-nitrobenzyl)isoquinoline. Neuropharmacological evaluation of the R and S isomers (by affinity to dopamine receptor sites in rat brain tissues, induction of stereotyped behavior, and interaction with motor arousal induced by (R)-apomorphine in the rat) indicated that, similar to the 10,11-dihydroxy congener 2, both enantiomers can bind to dopamine receptors but that only (R)-3 activates them, whereas (S)-3 shows activity as a dopaminergic antagonist.

Publication types

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

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Aporphines / chemical synthesis*
  • Aporphines / metabolism
  • Aporphines / pharmacology
  • Arousal / drug effects
  • Binding, Competitive
  • Chemical Phenomena
  • Chemistry
  • Corpus Striatum / metabolism
  • Dopamine Antagonists*
  • Male
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Stereoisomerism
  • Stereotyped Behavior / drug effects
  • Structure-Activity Relationship

Substances

  • Aporphines
  • Dopamine Antagonists
  • Receptors, Dopamine
  • 11-hydroxy-N-(n-propyl)noraporphine
  • Apomorphine