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The Search for Selective Dopaminergic Autoreceptor Agonists

  • S. Hjorth
  • A. Carlsson
  • D. Clark
  • K. Svensson
  • H. Wikström
  • D. Sanchez
  • P. Lindberg
  • U. Hacksell
  • L.-E. Arvidsson
  • A. Johansson
  • J. L. G. Nilsson
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 18)

Summary

In the course of a search for new selective dopamine (DA) autoreceptor agonists the DA analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, was resolved into its dextro-(+) and levo-(−) rotatory enantiomers. The compounds were pharmacologically evaluated by means of behavioural and biochemical methods. Surprisingly, both (+)- and (−)-3-PPP show clearcut, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA receptor agonist with activity on autoreceptors as well as postsynaptic receptors, whereas (−)-3-PPP similarly activates DA autoreceptors but, in contrast, concomitantly acts as an antagonist on postsynaptic DA receptors. Moreover, the behavioural/biochemical profile seems to indicate a preferential limbic action for the (−)-enantiomer. Such an action could be explained on the basis of different feedback arrangements in the nigrostriatal and mesolimbic DA systems and it is suggested that compounds such as (−)-3-PPP may find future clinical application as “second-generation” antipsychotic agents, lacking in the debilitating motor side effects produced by drugs in current therapeutic use.

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Copyright information

© Springer-Verlag Wien 1983

Authors and Affiliations

  • S. Hjorth
    • 4
  • A. Carlsson
    • 1
  • D. Clark
    • 1
  • K. Svensson
    • 1
  • H. Wikström
    • 2
  • D. Sanchez
    • 2
  • P. Lindberg
    • 2
  • U. Hacksell
    • 3
  • L.-E. Arvidsson
    • 3
  • A. Johansson
    • 3
  • J. L. G. Nilsson
    • 3
  1. 1.Department of PharmacologyUniversity of GöteborgGöteborgSweden
  2. 2.Org. Chem. Unit, Department of PharmacologyUniversity of GöteborgGöteborgSweden
  3. 3.Department of Org. Pharmaceut. Chem., Biomed. Ctr.University of UppsalaUppsalaSweden
  4. 4.Department of PharmacologyUniversity of GöteborgGöteborgSweden

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