To date, a number of potential, selective, central dopamine (DA) autoreceptor agonists have been presented (Figure 1). We were the first group to report on such a profile for racemic 3-PPP (Hjorth et al., 1980). That report was based upon data from our in vivo screening method which consists of a biochemical (DA synthesis rate) and a behavioral part (locomotor activity) assay. This gives the valuable information as to the pre-/postsynaptic relationship of the test compound. Interesting compounds are, of course, further tested in other biochemical and functional models to ascertain their pharmacological profile in greater detail. In these two basic models, racemic 3-PPP appears to be selective for DA autoreceptors since it decreases the DA synthesis rate without inducing any signs of locomotor activity in reserpinized rats. As the “3-PPP story” has developed, with resolution and extensive testing of the 3-PPP enantiomers, it now seems clear that R(+)-3-PPP is a classical DA receptor agonist with both pre-and postsynaptic agonist effects. S(−)-3-PPP is a partial agonist with an intrinsic efficacity of about 60% (striatum) in the biochemical (DA synthesis rate) γ-butyrolactone (GBL) model (acute DA autoreceptor agonist model). Table I gives the corresponding data for apomorphine and some other autoreceptor agonists.
KeywordsPartial Agonist Limbic System Synthesis Rate Ring Rotation Potential Energy Curve
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