Janssens de Varebeke P, Pauwels G, Buyse C, David-Remacle M, De Mey J, Roba J, Youdim M B
Searle European Development Centre, Continental Pharma, Inc., Mont-Saint-Guibert, Belgium.
J Neurochem. 1989 Oct;53(4):1109-16. doi: 10.1111/j.1471-4159.1989.tb07403.x.
The novel neuropsychotropic agent milacemide hydrochloride (2-n-pentylaminoacetamide HCl) is a highly selective substrate of the B form of monoamine oxidase (EC 1.4.3.4; MAO). Under the in vitro conditions used in the present study, milacemide acts as an enzyme-activated, partially reversible inhibitor of MAO-B. A reversible inhibition of MAO-A activity is also observed at high concentrations. The inhibitory activity of milacemide is significantly greater for MAO-B. In vivo, after single or repeated oral administration, a specific inhibition of MAO-B is apparent in brain and liver, with a lack of inhibition of the MAO-A activity. In contrast to the irreversible inhibitory action of L-deprenyl, the recovery of MAO-B activity in vivo after milacemide administration is significantly faster, a result suggesting that it is a partially reversible inhibitor. The selective inhibitory effect of milacemide for MAO-B in vivo is confirmed by its potentiation of phenylethylamine-induced stereotyped behavior, whereas vasopressor responses to tyramine were not affected. These observations suggest that milacemide could enhance dopaminergic activity in the brain and could be used as therapy for Parkinson's disease in association with L-3,4-dihydroxyphenylalanine.
新型神经精神药物盐酸米拉醋胺（2-正戊基氨基乙酰胺盐酸盐）是单胺氧化酶（EC 1.4.3.4；MAO）B型的高度选择性底物。在本研究使用的体外条件下，米拉醋胺作为一种酶激活的、部分可逆的MAO-B抑制剂发挥作用。在高浓度时也观察到对MAO-A活性的可逆抑制。米拉醋胺对MAO-B的抑制活性明显更强。在体内，单次或重复口服给药后，脑和肝中MAO-B受到特异性抑制，而MAO-A活性未受抑制。与L-司来吉兰的不可逆抑制作用相反，米拉醋胺给药后体内MAO-B活性的恢复明显更快，这一结果表明它是一种部分可逆的抑制剂。米拉醋胺在体内对MAO-B的选择性抑制作用通过其对苯乙胺诱导的刻板行为的增强作用得到证实，而对酪胺的升压反应未受影响。这些观察结果表明，米拉醋胺可增强脑中的多巴胺能活性，并可与L-3,4-二羟基苯丙氨酸联合用于帕金森病的治疗。
