Lajtha A, Sershen H, Cooper T, Hashim A, Gaál J
Nathan S. Kline Institute, Center for Neurochemistry Orangeburg, New York 10962, USA.
Neurochem Res. 1996 Oct;21(10):1155-60. doi: 10.1007/BF02532389.
We examined the cerebral metabolism of L-deprenyl and its fluoro-derivative pF-deprenyl, assaying the parent compounds, their metabolites desmethyl deprenyl, L-amphetamine, and L-methamphetamine, and the fluoro analogs of these metabolites. We compared the levels of the metabolites after subcutaneous injection with those after intracerebral administration (via microdialysis) of the parent compounds. The assay of the parent compounds and their metabolites was by GC-MS measurement of the components of brain microdialysate samples. After their subcutaneous administration, deprenyl and F-deprenyl rapidly entered the brain and then their concentration decreased, with an approximate half-life of 4.5 h. After the intracerebral administration the diffusion from the site of administration was minor. A small fraction (a few percent) of the intracerebrally administered deprenyl was metabolized in situ in the brain possibly by a nonenzymatic process. Metabolism of pF-deprenyl was somewhat more rapid. The higher cerebral levels of metabolites after the subcutaneous administration indicate their exogenous origin-metabolism of parent compounds in the periphery and penetration of the brain by the metabolites.
我们研究了左旋司来吉兰及其氟代衍生物对氟苯丙胺的脑代谢情况，分析了母体化合物、它们的代谢产物去甲基司来吉兰、L-苯丙胺和L-甲基苯丙胺，以及这些代谢产物的氟代类似物。我们比较了母体化合物皮下注射后与脑内给药（通过微透析）后代谢产物的水平。母体化合物及其代谢产物的分析是通过气相色谱-质谱法测定脑微透析液样本的成分。皮下给药后，司来吉兰和对氟苯丙胺迅速进入大脑，随后其浓度下降，半衰期约为4.5小时。脑内给药后，从给药部位的扩散很小。脑内给药的司来吉兰有一小部分（百分之几）可能通过非酶过程在脑内原位代谢。对氟苯丙胺的代谢稍快一些。皮下给药后代谢产物在脑中的水平较高，表明它们的外源性来源——母体化合物在外周代谢，代谢产物穿透大脑。
