Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP

Psychopharmacology (Berl). 1983;81(2):89-99. doi: 10.1007/BF00428999.


The two enantiomers of the putative centrally acting dopamine (DA) autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP (Hjorth et al. 1981), were pharmacologically evaluated. An extensive series of biochemical and behavioural experiments unexpectedly revealed that both (+)- and (-)-3-PPP showed clear, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA agonist with autoreceptor as well as postsynaptic receptor stimulatory properties. In contrast, although (-)-3-PPP similarly activates DA autoreceptors it acts concomitantly as an antagonist at postsynaptic DA receptors. Moreover, both behavioural and biochemical data on motor activity and DA synthesis and turnover suggest a preferential limbic action for the (-)-enantiomer. These results are discussed in terms of the dual antidopaminergic action of (-)-3-PPP coupled with anatomical differences in the feedback organisation in central (viz, limbic vs striatal) DA systems. It is suggested that compounds like (-)-3-PPP may be of potential clinical utility in the treatment of psychotic disorders, whilst lacking the seriously incapacitating motor dysfunctions produced by current neuroleptic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects
  • Biogenic Amines / metabolism
  • Brain Chemistry / drug effects
  • Dextroamphetamine / pharmacology
  • Male
  • Motor Activity / drug effects
  • Piperidines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Reserpine / pharmacology
  • Stereoisomerism


  • Biogenic Amines
  • Piperidines
  • Receptors, Dopamine
  • Reserpine
  • preclamol
  • Apomorphine
  • Dextroamphetamine