Luzindole, identified as N-0774, acts as a melatonin receptor blocker with a higher affinity for MT2 (Mel1b) receptors compared to MT1 (Mel1a), demonstrated by Ki values of 10.2 nM for MT2 and 158 nM for MT1. It has been found to inhibit the progression of experimental autoimmune encephalomyelitis (EAE) and display properties akin to antidepressants[1][2][3]. Additionally, Luzindole at concentrations ranging from 5-10 μg/ml effectively hinders the antigen-specific growth of the MBP-responsive LV-4 T cell line[1].
Luzindole 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Plasmodium falciparum 3D7
250 μM
5 h
inhibits UPS transcription modulation
J Pineal Res. 2012 Sep;53(2):147-53.
cardiomyocytes
10 μM
4 h
Luzindole effectively nullified melatonin-mediated cardioprotection of PS and ±dL/dt against APP/PS1 mutation without eliciting any effect on the controls.
Signal Transduct Target Ther. 2020 Jul 24;5(1):119.
DRG neurons
200 µM
24 h
Luzindole reversed the inhibitory effects of 8MP on MAPK1 and calcium channel expression but did not affect the inhibition by Mel.
Theranostics. 2017 May 12;7(7):2015-2032.
TC-1 cells
10 μM
24 h
Block melatonin receptor activity, inhibiting the protective effects of melatonin on H2O2-treated TC-1 cells
Exp Mol Med. 2019 Jul 4;51(7):1-12.
human granulosa-lutein cells
10 µM
24 h
To investigate the effect of luzindole on melatonin-stimulated aromatase expression and E2 production. Results showed that pretreatment with luzindole completely abolished melatonin-induced aromatase expression and E2 production.
Exp Mol Med. 2020 Aug;52(8):1341-1350.
rabbit embryos
420.0 ng/mL
block melatonin function, leading to increased ROS and 5-mC levels and decreased blastocyst rate
J Pineal Res. 2020 Apr;68(3):e12635.
human bone marrow-derived MSCs (BM-MSCs)
10 μM
4 days
Luzindole blocked melatonin-mediated anti-senescence effects by elevating the percentage of SA-β-gal-positive BM-MSCs and decreasing SIRT1 expression.
J Pineal Res. 2015 Sep;59(2):190-205.
VSC4.1 motoneurons
10 μM
20 min
Luzindole significantly attenuated melatonin-induced neuroprotection, suggesting that melatonin worked, at least in part, via its receptors to prevent VSC4.1 motoneuron apoptosis.
J Pineal Res. 2010 Mar;48(2):157-69.
bovine theca cells
10 μM
48 h
To investigate the effect of Luzindole on melatonin-induced STAR expression and progesterone production. Results showed that Luzindole significantly reduced melatonin-mediated increases in STAR expression and progesterone production.
Int J Biol Sci. 2019 Jan 1;15(2):404-415.
Luzindole 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Anesthetized rat duodenal mucosal HCO3- secretion model
Intravenous injection
600 nmol/kg
Single dose
Luzindole markedly inhibited the duodenal secretory response to intracerebroventricular phenylephrine.
J Clin Invest. 2001 Aug;108(4):625-33
C57BL/6J mice
Sciatic nerve cuffing model
Intraperitoneal injection
20 mg/kg
Once daily for 21 days
Luzindole blocked the inhibitory effects of 8MP on c-fos, CGRP, and inflammatory cytokine expression but did not affect the inhibition by Mel.
Theranostics. 2017 May 12;7(7):2015-2032.
ICR mice
OHSS model
Intraperitoneal injection
10 mg/kg
Once daily on days 4–6
To investigate the effect of luzindole on the development of OHSS. Results showed that luzindole treatment alleviated the symptoms of OHSS, including increased size of the ovary, body weight, and ovarian weight, and reduced aromatase expression and serum E2 levels.
Exp Mol Med. 2020 Aug;52(8):1341-1350.
C57BL/6 mice
Myocardial infarction model
Intraperitoneal injection
1 mg/kg
Once daily for 14 days
Luzindole blocked the promoting effect of melatonin on cardiomyocyte proliferation and cardiac regeneration
Acta Pharmacol Sin. 2021 Jun;42(6):921-931
Luzindole 动物研究
Animal study
Administering Luzindole at a dose of 30 mg/kg intraperitoneally from day 0 to day 5 has been shown to suppress experimental autoimmune encephalomyelitis[2]. Luzindole administered at 30 mg/kg intraperitoneally is observed to decrease immobility time in a dose-responsive manner, with a more significant effect at midnight, showing a 60% reduction, compared to a 39% reduction at noon. The peak impact of luzindole occurs at 60 minutes. However, the anti-immobility influence of luzindole at 10 mg/kg is counteracted by melatonin at 30 mg/kg. In albino ND/4 mice or C57BL/6J mice, which lack melatonin production, luzindole at 30 mg/kg does not alter immobility times at either noon or midnight[3].
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