同义名 :	-
	CAS号 :	342652-67-9
	货号 :	A899895
	分子式 :	C17H20N8O2
	纯度 :	99%
	分子量 :	368.39
	MDL号 :	MFCD18086893
	存储条件：	Pure form Inert atmosphere, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

MRK-016 is a pyrazolotriazine with an affinity of between 0.8 and 1.5 nM for the benzodiazepine binding site of native rat brain and recombinant human alpha1-, alpha2-, alpha3-, and alpha5-containing GABA(A) receptors. It has inverse agonist efficacy selective for the alpha5 subtype. MRK-016 gave good receptor occupancy after oral dosing in rats, with the dose required to produce 50% occupancy being 0.39 mg/kg and a corresponding rat plasma EC(50) value of 15 ng/ml that was similar to the rhesus monkey plasma EC(50) value of 21 ng/ml obtained using [(11)C]flumazenil positron emission tomography. In normal rats, MRK-016 enhanced cognitive performance in the delayed matching-to-position version of the Morris water maze but was not anxiogenic, and in mice it was not proconvulsant and did not produce kindling. MRK-016 had a short half-life in rat, dog, and rhesus monkey (0.3-0.5 h) but had a much lower rate of turnover in human compared with rat, dog, or rhesus monkey hepatocytes[3]. MRK (MRK-016) can prevent LPS- induced cognitive deficits associated with elevated Aβ, and restore hippocampal BDNF expression[4].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.71mL 0.54mL 0.27mL	13.57mL 2.71mL 1.36mL	27.15mL 5.43mL 2.71mL

参考文献

[1]Eimerbrink MJ, White JD, et al. Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin. Behav Brain Res. 2015 Jul 15;288:50-3. [2]Atack JR, Maubach KA, et al. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)- pyrazolo[1,5-d] -[1,2,4] triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84. [3]Atack JR, Maubach KA, Wafford KA, O'Connor D, Rodrigues AD, Evans DC, Tattersall FD, Chambers MS, MacLeod AM, Eng WS, Ryan C, Hostetler E, Sanabria SM, Gibson RE, Krause S, Burns HD, Hargreaves RJ, Agrawal NG, McKernan RM, Murphy MG, Gingrich K, Dawson GR, Musson DG, Petty KJ. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84 [4]Eimerbrink MJ, Pendry RJ, Hodges SL, Wiles JD, Peterman JL, White JD, Hayes HB, Chumley MJ, Boehm GW. The α5-GABAAR inverse agonist MRK-016 upregulates hippocampal BDNF expression and prevents cognitive deficits in LPS-treated mice, despite elevations in hippocampal Aβ. Behav Brain Res. 2019 Feb 1;359:871-877