McKenna K F, Baker G B, Coutts R T, Rauw G, Mozayani A, Danielson T J
Neurochemical Research Unit, University of Alberta, Edmonton, Canada.
J Neural Transm Suppl. 1990;32:113-8. doi: 10.1007/978-3-7091-9113-2_15.
Although N2-acetylphenelzine (N2AcPLZ) appears to be only a minor metabolite of phenelzine (PLZ), other investigations have demonstrated that it may be worthy of study as an antidepressant in its own right. In the present report, the possibility of ring hydroxylation as a metabolic route for PLZ was investigated in the rat. Indirect evidence for such a route was obtained using iprindole, a drug known to block ring hydroxylation. Treatment of rats with iprindole followed by PLZ was demonstrated to result in increased brain levels of PLZ and beta-phenylethylamine (control rats were treated with vehicle and then PLZ). The possibility that hydroxylation in the para-position might be a metabolic route for PLZ has led to interest in the possible use of analogues in which this position is blocked with a substituent. In preliminary acute studies at a dose of 0.1 mmol/kg p-chloro-PLZ was found to have a similar effect to PLZ on the inhibition of MAO and to lead to an elevation of catecholamines and 5-hydroxytryptamine (5-HT) in rat whole brain.
虽然N2-乙酰苯乙肼（N2AcPLZ）似乎只是苯乙肼（PLZ）的一种次要代谢产物，但其他研究表明，它本身作为一种抗抑郁药可能值得研究。在本报告中，研究了大鼠体内PLZ的环羟基化作为一种代谢途径的可能性。使用异吲哚（一种已知可阻断环羟基化的药物）获得了这种途径的间接证据。给大鼠注射异吲哚后再注射PLZ，结果显示大鼠脑内PLZ和β-苯乙胺水平升高（对照大鼠先注射赋形剂再注射PLZ）。对位羟基化可能是PLZ的一种代谢途径，这使得人们对该位置被取代基阻断的类似物的可能用途产生了兴趣。在剂量为0.1 mmol/kg的初步急性研究中，发现对氯-PLZ对MAO的抑制作用与PLZ相似，并导致大鼠全脑儿茶酚胺和5-羟色胺（5-HT）水平升高。
