The effects of SCH 23390, YM 09151-2, (+)- and (-)-3-PPP and some classical neuroleptics on D-1 and D-2 receptors in rat neostriatum in vitro

Eur J Pharmacol. 1984 Oct 1;105(1-2):73-83. doi: 10.1016/0014-2999(84)90650-2.

Abstract

The actions in vitro of SCH 23390, YM 09151-2 and both enantiomers of 3-PPP on D-1 and D-2 dopamine receptors were investigated in superfused rat neostriatal slices. For comparison the following neuroleptics of different chemical classes were incorporated in our investigations: (+)-bulbocapnine, clozapine, chlorpromazine, cis-flupenthixol, (-)-sulpiride and haloperidol. The increase in the efflux of cyclic AMP was used as a measure for D-1 receptor stimulation. The decrease in the K+-evoked release of [3H]acetylcholine was used as measure of D-2 receptor stimulation. None of the drugs stimulated the D-1 receptor. Only (+)-3-PPP stimulated the D-2 receptor. All other drugs, including (-)-3-PPP, behaved as antagonists on the D-2 receptor, YM 09151-2 being the most potent. SCH 23390 was the most potent antagonist on the D-1 receptor. Haloperidol, cis-flupenthixol and (+)-bulbocapnine showed an appreciable D-1 receptor blocking potency in our model, whereas the other drugs were inactive. We found SCH 23390 to be the most D-1 selective antagonist although the drug still displayed considerable potency on the D-2 receptor. YM 09151-2 was the most D-2 selective antagonist.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Acetylcholine / metabolism
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Aporphines / pharmacology
  • Benzamides / pharmacology*
  • Benzazepines / pharmacology*
  • Caudate Nucleus / drug effects*
  • Caudate Nucleus / metabolism
  • Chlorpromazine / pharmacology
  • Clozapine / pharmacology
  • Flupenthixol / pharmacology
  • Haloperidol / pharmacology
  • In Vitro Techniques
  • Male
  • Piperidines / pharmacology*
  • Potassium / pharmacology
  • Putamen / drug effects*
  • Putamen / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine / metabolism
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2

Substances

  • Antipsychotic Agents
  • Aporphines
  • Benzamides
  • Benzazepines
  • Piperidines
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • preclamol
  • Flupenthixol
  • Clozapine
  • Haloperidol
  • Acetylcholine
  • nemonapride
  • Potassium
  • 1-Methyl-3-isobutylxanthine
  • Chlorpromazine