Pre- and postsynaptic dopaminergic activities of indolizidine and quinolizidine derivatives of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP). Further developments of a dopamine receptor model

J Med Chem. 1990 Mar;33(3):1015-22. doi: 10.1021/jm00165a020.


Pre- and postsynaptic dopaminergic activities of a series of indolizidine and quinolizidine analogues of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP) have been studied. The pharmacological data have been interpreted in terms of a previously reported model for interactions with dopamine pre- and postsynaptic D2-receptors and molecular mechanics (MM2(85] calculated geometries and conformational energies. The model has been further developed with respect to the receptor topography in the vicinity of the nitrogen binding site. In particular, a novel spatial orientation of the important "propyl cleft" has been proposed. This cleft is suggested to be located mainly above a plane through the receptor-bound substrate. The biologically active agonist and antagonist conformations of the enantiomers of 3-PPP have been reinvestigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • 5-Hydroxytryptophan / metabolism
  • Animals
  • Dopamine Agents / chemical synthesis
  • Dopamine Agents / pharmacology*
  • Dopamine Antagonists
  • Male
  • Models, Structural
  • Molecular Conformation
  • Motor Activity / drug effects
  • Piperidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Structure-Activity Relationship


  • Dopamine Agents
  • Dopamine Antagonists
  • Piperidines
  • Receptors, Dopamine
  • 3,4-Dihydroxyphenylacetic Acid
  • preclamol
  • 5-Hydroxytryptophan