Enantiomers of 3-(3,4-dihydroxyphenyl)- and 3-(3-hydroxyphenyl)-N-n-propylpiperidine: central pre- and postsynaptic dopaminergic effects and pharmacokinetics

J Med Chem. 1986 Oct;29(10):1889-95. doi: 10.1021/jm00160a016.


This study emphasizes the importance of the metabolic conversion of the enantiomers of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) into their catechol analogues, the enantiomers of 3-(3,4-dihydroxyphenyl)-N-n-propylpiperidine. These isomers are both shown to be excellent substrates for COMT, with a slight preference for the S-(-) enantiomer. Assessment of the dopaminergic activity of these catechols and the results from the determination of brain levels of the enantiomers of 3-PPP and their metabolites indicate that the metabolites probably do not alter the pharmacological profiles established for (R)-(+)- and (S)-(-)-3-PPP. The conversion of the monophenols into catecholic metabolites is only 1-5%, and the further conversion of these catecholic metabolites into methoxylated analogues is very rapid. However, the very interesting observation was made that, when inhibiting COMT by means of tropolone and subsequently treating the rats with high doses of (S)-(-)-3-PPP (ip), postsynaptic dopaminergic activity was elicited. This has never been seen for (S)-(-)-3-PPP without tropolone pretreatment and might indicate that, in this special case, the catecholic metabolite affects the in vivo pharmacological profile of (S)-(-)-3-PPP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Kinetics
  • Male
  • Methylation
  • Motor Activity / drug effects
  • Piperidines / metabolism
  • Piperidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Stereoisomerism


  • Piperidines
  • Receptors, Dopamine
  • 3-(3,4-dihydroxyphenyl)-N-n-propylpiperidine
  • preclamol