- 生物活性
Lazabemide (Ro 19-6327) 是单胺氧化酶 B (MAO-B) 的选择性的可逆抑制剂 (IC50=0.03 μM)，但对 MAO-A (IC50>100 μM) 活性较低。高浓度 Lazabemide 具有抑制单胺摄取的作用，抑制去甲肾上腺素、血清素和多巴胺摄取的 IC50 值分别为 86 μM、123 μM 和 >500 μM。Lazabemide 可用于帕金森和阿尔茨海默病的研究。
- 靶点
IC50: 30 nM (MAO-B).
- 体外研究
The in vitro binding characteristics of both radiolabeled inhibitors revealed them to be selective, high-affinity ligands for the respective enzymes. K
D
and B
max
values for
3
H-Ro 19-6327 in rat cerebral cortex are 18.4 nM and 3.45 pmol/mg protein, respectively. The IC
50
values for lazabemide are: 86 μM for NA uptake; 123 μM for 5HT uptake; > 500 μM for DA uptake, respectively.. Lazabemide (5 μM) inhibits human MAO-B and MAO-A with IC
50
of 6.9 nM and >10 nM, respectively. And it inhibits rat MAO-B and MAO-A with IC
50
of 37 nM and >10 μM, respectively ina enzymatic assay.Lazabemide differs from L-deprenyl in their ability to induce release of endogenous monoamines from synaptosomes. Thus, Lazabemide (500 μM) induces a greater 5 HT release than does L-deprenyl, but is less effective than L-deprenyl in releasing DA. On the contrary, lazabemide was almost completely inactive on either 5-HT and DA release. Lazabemide (250 nM) results in a clear inhibition of DOPAC formation, while does not increase the accumulation of newly-formed DA in those tubular epithelial cells loaded with 50 microM L-DOPA.
- 体内研究
Lazabemide (3 mg/kg) attenuates ichemia reperfusion-induced hydroxyl radical generation and pretreatment with Lazabemide showed decreased DOPAC levels in comparison with those of their respective vehicle-treated control groups.
- 化学性质
单盐酸拉扎贝胺(Lazabemide Monohydrochloride)：C8Hl0ClN3OHCl。[103878-83-7]。从甲醇-乙醚结晶，熔点193～195℃。分配系数(正辛醇脉)：约0.1。pKa 8.9。急性毒性LD
50
小鼠(mg/kg)：1000~2000口服。
- 抗帕金森病药。为作用于脑内和外周器官的选择性可逆的单胺氧化酶B(MAO-B)抑制剂。
医药
5-氯吡啶2-羧酸(I)和N-(2-氨基乙基)氨基甲酸叔丁酯(Ⅱ)，在羰二咪唑(CDI)存在下，在四氢呋喃中回流，得到化合物(II)。再和三氟乙酸在二氯甲烷中回流水解，然后用乙醇盐酸处理，得到单盐酸拉扎贝胺。
