根据一项对小鼠的研究，哺乳动物可能通过类似于植物生物合成吗啡的生物化学路径而在体内天然制造吗啡。Meinhart Zenk及其同事向小鼠注射了标记的和未标记的潜在吗啡前体，诸如四氢巴马汀（THP），然后分析了小鼠的尿液。

此前的研究显示人类和小鼠在尿液中分泌少量的吗啡，但是科学家仍然不确定这种化学物质是否以及如何在体内产生。这组作者检验了小鼠尿液含有吗啡以及在它们的体内形成的相关化合物。

对标记的分子的分析排除了吗啡的饮食来源，表明了小鼠把THP代谢成了吗啡，其过程类似于此前在罂粟中观察到的吗啡生产路径。这组作者提处，通过尿液分泌的吗啡分子逃避了在器官和组织中的进一步修饰，这可能提供动物如何代谢这种化学物质的一幅快照。这组作者说，这项研究可能有助于确定吗啡和类似化合物在人体中的作用，这可能帮助疼痛和药物依赖性研究。

原文出处：

PNAS doi: 10.1073/pnas.1003423107

Urinary excretion of morphine and biosynthetic precursors in mice
Nadja Grobea,1, Marc Lamshftb,1, Robert G. Orthc, Birgit Dr gerd, Toni M. Kutchana, Meinhart H. Zenka,2,3, and Michael Spitellerb,2

aDonald Danforth Plant Science Center, 975 North Warson Road, St. Louis, MO 63132;
bInstitute of Environmental Research, University of Technology Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany;
cApis Discoveries LLC, 5827 Buffalo Ridge Road, P.O. Box 55, Gerald, MO 63037; and
dInstitute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Hoher Weg 8, 06120 Halle, Germany

It has been firmly established that humans excrete a small but steady amount of the isoquinoline alkaloid morphine in their urine. It is unclear whether it is of dietary or endogenous origin. There is no doubt that a simple isoquinoline alkaloid, tetrahydropapaveroline (THP), is found in human and rodent brain as well as in human urine. This suggests a potential biogenetic relationship between both alkaloids. Unlabeled THP or [1,3,4-D3]-THP was injected intraperitoneally into mice and the urine was analyzed. This potential precursor was extensively metabolized (96%). Among the metabolites found was the phenol-coupled product salutaridine, the known morphine precursor in the opium poppy plant. Synthetic [7D]-salutaridinol, the biosynthetic reduction product of salutaridine, injected intraperitoneally into live animals led to the formation of [7D]-thebaine, which was excreted in urine. [N-CD3]-thebaine was also administered and yielded [N-CD3]-morphine and the congeners [N-CD3]-codeine and [N-CD3]-oripavine in urine. These results show for the first time that live animals have the biosynthetic capability to convert a normal constituent of rodents, THP, to morphine. Morphine and its precursors are normally not found in tissues or organs, presumably due to metabolic breakdown. Hence, only that portion of the isoquinoline alkaloids excreted in urine unmetabolized can be detected. Analysis of urine by high resolution-mass spectrometry proved to be a powerful method for tracking endogenous morphine and its biosynthetic precursors.