DISODIUM 2'-[4-[[2,6-DIHYDROXY-3-[(4-SULPHONATOPHENYL)AZO]PHENYL]AZO]PHENYL]-6-METHYL[2,6'-BIBENZOT; 2'-[4-[[2,6-Dihydroxy-3-[(4-sulfophenyl)azo]phenyl]azo]phenyl]-6-methyl-2,6'-bibenzothiazole-7-sulfonic acid disodium salt; C.I.20210; C.I.Direct Brown 80; Direct Brown 80
酸性蓝90; 酸性艳蓝G; 亮蓝G; 考马士亮兰G-250; 考马斯亮兰G250; 康美赛蓝G250; 3-(((4-((4-((4-乙氧基苯基)氨基)苯基)(4-(乙基(3-磺酰苄基)亚氨基)-2-甲基环己-2,5-二烯-1-亚基)甲基)-3-甲基苯基)(乙基)氨基)甲基)苯磺酸钠; Acid Blue 90; CBB G-250; Cyanine G; PAGE BLUE G90; Coomassie Brilliant blue; Polar Blue G; Blue G 250; BRILLIANT BLUE; SERVA BLUE G; Brilliant Blue G; Sodium 3-(((4-((4-((4-ethoxyphenyl)amino)phenyl)(4-(ethyl(3-sulfonatobenzyl)iminio)-2-methylcyclohexa-2,5-dien-1-ylidene)methyl)-3-methylphenyl)(ethyl)amino)methyl)benzenesulfonate
酸性艳蓝; 考马斯亮蓝G250; 考马士亮兰G-250; 考马斯亮兰G250; 亮蓝G; 酸性艳蓝G; 食用蓝色1号; 食用蓝色2号; 康美赛蓝G250; abcolbrilliantcyanineblueg; Coomassie Brilliant Blue G250; SERVA BLUE G; CBB G-250; Cyanine G; PAGE BLUE G90; coomassie briliant blue G-250; coomassie blue G-250; Coomassie Brilliant blue; Polar Blue G; Blue G 250; BRILLIANT BLUE; coomassie brillant blue G
- 生物活性
N-Desmethylclozapine 是非典型抗精神病药 Clozapine 的主要活性代谢产物。N-Desmethylclozapine 是一种有效的、变构的部分 M1 受体激动剂 (EC50=115 nM)，能通过 M1 受体激活增强海马 N-methyl-d-aspartate (NMDA) 受体电流。N-Desmethylclozapine 也是 δ-opioid 激动剂。
- 靶点
EC50: 115 nM (M1 receptors)
δ-opioid
- 体外研究
The brain penetrant metabolite N-desmethylclozapine preferentially bound to M1 muscarinic receptors with an IC
50
of 55 nM and was a more potent partial agonist (EC
50
, 115 nM and 50% of acetylcholine response) at this receptor than clozapine.
N-desmethylclozapine exhibits slight agonistic effects on the M1 mAChR, and agonistic properties at the 5-HT1A receptor in the cerebral cortex and hippocampus. This compound also behaves as an agonist at the δ-opioid receptor in the cerebral cortex and striatum.
N-desmethylclozapine (3 μM) greatly decreases the outward current in excitatory neurons, but not in inhibitory neurons. In excitatory neurons, N-desmethylclozapine alone is more effective than either clozapine alone or the combination of clozapine and N-desmethylclozapine. The effect of N-desmethylclozapine in excitatory neurons is significantly suppressed by 0.1 μM pirenzepine and 1 μM atropine. N-desmethylclozapine, but not clozapine, suppressed K
+
channels via M1 receptors in excitatory cells.
N-desmethylclozapine leads to a decrease in TxB2 levels under unstimulated conditions as well as under TSST-1 stimulation. Clozapine, N-desmethylclozapine and CPZ possibly act on neurotransmitter systems via modulation of TxA2 or TxB2 production.
The IC
50
s of N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate in Huh-7 cells infected with DENV-2 are 1 μM, 0.38 μM, and 0.67 μM, respectively. The levels of NS3 are reduced in cells treated with all three inhibitors compared to DMSO treatment, suggesting that the inhibitors act at a stage prior to viral protein translation. N-Desmethylclozapine-treated cells show a >75% reduction in negative-strand RNA levels.
- 体内研究
N-desmethylclozapine in rat and human at M2 and M4 mAChRs underlying presynaptic modulation of GABA and glutamate release, respectively. In particular, N-desmethylclozapine maybe a M2 mAChR antagonist in the rat but has no activity at this receptor in human neocortex. However, N-desmethylclozapine has an agonistic effect at M4 mAChR in the human but no such effect in the rat neocortex.
