In vivo displacement by 3-PPP enantiomers of N,N-dipropyl-5,6-ADTN from dopamine receptor-binding sites in rat striatum.

The enantiomers of 3-PPP or haloperidol were injected in various doses to rats 1 hour after the established dopamine receptor ligand N,N-dipropyl-5,6-ADTN. After another 40 minutes the binding of the ligand to the striatum was measured by high performance liquid chromatography, using the level in the cerebellum as "blank". (-)-3-PPP was found to cause a maximum 71% displacement of the ligand from the striatal binding sites. Haloperidol proved to be more potent but not significantly more efficacious in displacing the ligand. However, the combined treatment with (-)-3-PPP and haloperidol caused a stronger displacement of the ligand than (-)-3-PPP alone, suggesting that the binding-site populations available for the two agents are not fully identical. (+)-3-PPP also caused displacement of the ligand but was considerably less potent than its enantiomeric twin. The results are discussed against the background of the different pharmacological profiles of the 3-PPP enantiomers and haloperidol. It is suggested that an inverse relationship may exist between receptor affinity and intrinsic activity and that such a relationship may be inherent in the mechanism underlying receptor stimulation.