Rollema H, Mastebroek D, Wikström H, Horn A S
J Pharm Pharmacol. 1985 May;37(5):314-9. 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 Km and Vmax values of about 1 microM 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 mumol 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.
多巴胺激动剂3-PPP及其对映体在体外被大鼠肝微粒体羟基化为儿茶酚胺3-(3,4-二羟基苯基)-N-正丙基哌啶(4-OH-3-PPP)，其Km和Vmax值分别约为1 microM和2 nmol (mg蛋白)-1 min-1。由于形成的儿茶酚胺似乎是儿茶酚-O-甲基转移酶的良好底物，只有在通过托酚酮抑制COMT后才能检测到大鼠体内由3-PPP形成的儿茶酚胺。给药45分钟后，通过高效液相色谱-电化学检测法测得的脑中4-OH-3-PPP水平，腹腔注射45 μmol kg-1 3-PPP后约为350 pmol g-1，皮下注射后约为100 pmol g-1，外消旋体、(+)或(-) 3-PPP之间无显著差异。据估计，这些儿茶酚胺水平在腹腔注射3-PPP后约占3-PPP水平的1-5%，皮下注射后约占0.2-0.5%。讨论了3-PPP的这种代谢转化与其药理学特性的相关性。
