Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors
Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors
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DOI：
10.1016/s0006-2952(00)00306-3
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发表时间：
2000-06-15
影响因子：
5.8
通讯作者：
Wurtman, RJ
中科院分区：
文献类型：
--
作者：
Ulus, IH;Maher, TJ;Wurtman, RJ
芬特明在20世纪70年代被证明通过单胺氧化酶（MAO）抑制5-羟色胺的代谢，但从未被标记为MAO抑制剂;因此，它被广泛用于与芬氟拉明组合，并继续使用，违反其标签，与其他5-羟色胺摄取阻滞剂。我们研究了芬特明和其他几种未标记的MAO抑制剂对大鼠肺，脑和肝脏中MAO活性的影响，以及这些药物一起给药时的相互作用。使用5-羟色胺和β-苯乙胺作为底物，测定大鼠组织的MAO-A和-B。芬特明抑制所有三种组织中的马洛宁代谢（MAO-A）活性，Ki值为85-88 μ M。这些效力与抗抑郁剂单胺氧化酶抑制剂异丙烟肼和吗氯贝胺相似。当芬特明与其他未标记的可逆性MAO抑制剂（如伪麻黄碱，麻黄碱，去甲麻黄碱;苯甲酸雌二醇）混合时，MAO抑制的程度是相加的。据报道，与芬氟拉明-芬特明使用相关的心脏瓣膜病变和原发性肺动脉高压可能是由5-羟色胺摄取和代谢的间歇性并发阻滞引起的（C）2000 Elsevier Science Inc.
Phentermine was shown in the 1970s to inhibit the metabolism of serotonin by monoamine oxidase (MAO), but never was labeled as an MAO inhibitor; hence, it was widely used in combination with fenfluramine, and continues to be used, in violation of their labels, with other serotonin uptake blockers. We examined the effects of phentermine and several other unlabeled MAO inhibitors on MAO activities in rat lung, brain, and liver, and also the interactions of such drugs when administered together. Rat tissues were assayed for MAO-A and -B, using serotonin and beta-phenylethylamine as substrates. Phentermine inhibited serotonin-metabolizing (MAO-A activity in all three tissues with K-i values of 85-88 mu M. These potencies were similar to those of the antidepressant MAO inhibitors iproniazid and moclobemide. When phentermine was mixed with other unlabeled reversible MAO inhibitors (e.g. pseudoephedrine, ephedrine, norephedrine; estradiol benzoate), the degree of MAO inhibition was additive. The cardiac valvular lesions and primary pulmonary hypertension that have been reported to be associated with fenfluramine-phentermine use may have resulted from the intermittent concurrent blockage of both serotonin uptake and metabolism (C) 2000 Elsevier Science Inc.