NeuroSearch Sweden AB, Arvid Wallgrens Backe 20, S-413 46 Göteborg, Sweden.
J Med Chem. 2012 Apr 12;55(7):3242-9. doi: 10.1021/jm201692d. Epub 2012 Mar 23.
A series of para-substituted 4-phenylpiperidines/piperazines have been synthesized and their affinity to recombinant rat cerebral cortex monoamine oxidases A (MAO A) and B (MAO B) determined. Para-substituents with low dipole moment increased the affinity to MAO A, whereas groups with high dipole moment yielded compounds with no or weak affinity. In contrast, the properties affecting MAO B affinity were the polarity and bulk of the para-substituent, with large hydrophobic substituents producing compounds with high MAO B affinity. In addition, these compounds were tested in freely moving rats and the effect on the post-mortem neurochemistry was measured. A linear correlation was demonstrated between the affinity for MAO A, but not MAO B, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) in the striatum.
一系列对位取代的 4-苯基哌啶/哌嗪已被合成，并测定了它们对重组大鼠大脑皮质单胺氧化酶 A（MAO A）和 B（MAO B）的亲和力。具有低偶极矩的对位取代基增加了对 MAO A 的亲和力，而具有高偶极矩的基团则产生无或弱亲和力的化合物。相比之下，影响 MAO B 亲和力的性质是对位取代基的极性和体积，大的疏水性取代基产生对 MAO B 具有高亲和力的化合物。此外，这些化合物在自由活动的大鼠中进行了测试，并测量了对死后神经化学的影响。结果表明，MAO A 的亲和力与 3,4-二羟基苯乙酸（DOPAC）和 3-甲氧基酪胺（3-MT）在纹状体中的水平之间存在线性相关性，但 MAO B 的亲和力则没有。
