Colombo M, Strolin Benedetti M, Bonsignori A, Cocchiara G, Roncucci R, Dostert P
Research and Development, Erbamont Group, Farmitalia Carlo Erba, Milan, Italy.
J Neural Transm Suppl. 1990;32:123-9. doi: 10.1007/978-3-7091-9113-2_17.
Milacemide was found to protect Swiss albino CD1 mice but not Sprague Dawley rats against bicuculline-induced lethality. Since it had been previously suggested that the anticonvulsant activity of milacemide might be related to MAO-B- mediated glycine formation, brain and liver MAO-A and-B activities and the urinary metabolic pattern of milacemide were determined in the same mice and rat strains. Similar brain and liver MAO activities were found in the two species, except for liver MAO-A activity which was higher in rats. After the same oral dose of milacemide, the percent of the dose excreted as glycinamide was significantly higher in mice than in rats, whereas that excreted as metabolite UK1 was significantly higher in rats. These results support the hypothesis of a glycine-mediated anticonvulsant activity for milacemide and suggest that the increased formation of UK1 to the detriment of glycinamide might account for the lack of protection against bicuculline-induced lethality by milacemide in rats.
已发现米那米特可保护瑞士白化病CD1小鼠，但不能保护斯普拉格-道利大鼠免受荷包牡丹碱诱导的致死作用。由于此前有人提出米那米特的抗惊厥活性可能与单胺氧化酶B（MAO-B）介导的甘氨酸形成有关，因此在相同的小鼠和大鼠品系中测定了脑和肝中MAO-A和MAO-B的活性以及米那米特的尿代谢模式。在这两个物种中发现了相似的脑和肝MAO活性，但大鼠的肝MAO-A活性较高。给予相同口服剂量的米那米特后，以甘氨酰胺形式排泄的剂量百分比在小鼠中显著高于大鼠，而以代谢物UK1形式排泄的剂量百分比在大鼠中显著更高。这些结果支持了米那米特具有甘氨酸介导的抗惊厥活性这一假说，并表明UK1生成增加而甘氨酰胺生成减少可能是米那米特对大鼠荷包牡丹碱诱导的致死作用缺乏保护的原因。
