In-vitro and in-vivo metabolism of the presynaptic dopamine agonist 3-PPP to a catecholic analogue in rats

Article abstract of DOI:10.1111/j.2042-7158.1985.tb05073.x

The dopamine agonist 3-PPP and its enantiomers are hydroxylated in-vitro by rat liver microsomes to the catecholamine 3-(3,4-dihydroxyphenyl)-N-n-propylpiperidine (4-OH-3-PPP) with K(m) and V(max) values of about 1 μM and 2 nmol (mg protein)^-1 min^-1 respectively. As the catecholamine formed appears to be a good substrate for catechol-O-methyltransferase, in-vivo catecholamine formation in rats from 3-PPP was only detectable after inhibition of COMT by tropolone. The resulting brain levels of 4-OH-3-PPP, as measured by HPLC with electrochemical detection 45 min after administration, were about 350 pmol g^-1 after i.p., and about 100 pmol g^-1 after s.c. injection of 45 μol kg^-1 3-PPP, with no significant difference between racemic, (+) or (-) 3-PPP. It was estimated that these catecholamine levels represent about 1-5% of the 3-PPP levels after i.p., and about 0.2-0.5% after s.c. administration of 3-PPP. The relevance of this metabolic conversion of 3-PPP for its pharmacological profile is discussed.