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.
