Haber H, Roske I, Rottmann M, Georgi M, Melzig M F
Research Institute of Molecular Pharmacology, Berlin, Germany.
Life Sci. 1997;60(2):79-89. doi: 10.1016/s0024-3205(96)00597-8.
Dopamine-derived alkaloids, the tetrahydroisoquinolines (TIQs), are suspected to play a role in the pathogenesis of alcoholism. The present study describes the alcohol induced formation of the S-enantiomer of Tetrahydropapaveroline and Norcoclaurine in the rat brain. These compounds are of special interest since both were found as being intermediates in the biosynthesis of morphine in the opium poppy. The concentration of both TIQs were determined in different brain regions of Wistar rats after 6 and 18 months alcohol consumption ad libitum. Gas chromatography/mass spectrometry was used for the detection and quantification of the enantiomers. Tetrahydropapaveroline and norcoclaurine were detected only in the striatum of those rats which had consumed alcohol for 18 month, neither in other brain regions nor in any brain regions of the controls or the short term (6 month) alcohol treated rats. These findings and the fact that those tetrahydroisoquinolines were only detected in the striatum of the alcohol fed rats and were present only as the S-enantiomers suggest that an alcohol induced biosynthetic pathway exists in the mammalian brain.
多巴胺衍生的生物碱，即四氢异喹啉（TIQs），被怀疑在酒精中毒的发病机制中起作用。本研究描述了酒精诱导大鼠脑中四氢罂粟碱和去甲乌药碱的S-对映体的形成。这些化合物特别令人感兴趣，因为它们在罂粟中吗啡的生物合成过程中均被发现是中间体。在自由摄取酒精6个月和18个月后，测定了Wistar大鼠不同脑区中这两种TIQs的浓度。采用气相色谱/质谱法检测和定量对映体。仅在饮酒18个月的大鼠纹状体中检测到四氢罂粟碱和去甲乌药碱，在其他脑区以及对照组或短期（6个月）酒精处理大鼠的任何脑区中均未检测到。这些发现以及仅在饮酒大鼠的纹状体中检测到那些四氢异喹啉且仅以S-对映体形式存在这一事实表明，哺乳动物脑中存在酒精诱导的生物合成途径。
