MRK-016 是一种选择性的，可口服的，可透过血脑屏障的 GABA_A α5 receptor 拮抗剂，对 GABA_A α5 的 EC₅₀ 值为 3 nM，对人 GABA_A α1β3γ2，GABA_A α2β3γ2，GABA_A α3β3γ2 和 GABA_A α5β3γ2 的 K_i 值分别为 0.83，0.85，0.77 和 1.4 nM。

MRK-016 is a selective, orally bioavailable inverse agonist of GABA A α5 receptor, with an EC 50 of 3 nM for GABA A α5, and K i s of 0.83, 0.85, 0.77?and 1.4?nM for human?GABA A ?α1β3γ2, GABA A ?α2β3γ2, GABA A ?α3β3γ2, and GABA A ?α5β3γ2, respectively; MRK-016 also readily penetrates the CNS.

Solid

EC50: 3 nM (GABAA α5)
Ki: 0.83?nM (Human?GABAA?α1β3γ2), 0.85?nM (Human?GABAA?α2β3γ2), 0.77?nM (Human?GABAA?α3β3γ2), 1.4?nM (Human?GABAA?α5β3γ2)

MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77?and 1.4?nM for human?GABAA?α1β3γ2, GABAA?α2β3γ2, GABAA?α3β3γ2, and GABAA?α5β3γ2, respectively. MRK-016 is a full inverse agonist at the α5-subtype, shows very weak affinity at the GABAA α4β3γ2-subtype (Ki 395 ± 173 nM) and is essentially inactive at the GABAA α6β3γ2 receptor (Ki > 4000 nM). MRK-016 shows a weak effect on GABAA?α4β3γ2 with a Ki of 400 nM. MRK-016 (100 nM) alao increases long-term potentiation in mouse hippocampal slices. has not independently confirmed the accuracy of these methods. They are for reference on

MRK-016 does not enhance pentylenetetrazole-induced convulsions at 10 mg/kg via ip, or cause seizures at 30 mg/kg, via po for 20 days in mice. MRK-016 shows no obvious anxiogenic-like effects in rats at doses that occupy >95% of benzodiazepine (BZ) binding sites. MRK-016 (0.3, 1, and 3 mg/kg, p.o.) dose-dependently improves performance of rats hippocampal-dependent memory task. MRK-016 (0.3-30 mg/kg, p.o.) causes good receptor occupancy in rats. MRK-016 (0.3, 1, or 3 mg/kg p.o.) shows cognition-enhancing activity in the delayed matching-to-position version of the Morris water maze. MRK-016 (1, 3, or 10 mg/kg i.p.) does not produce kindling in mice. MRK-016 (3 mg/kg, i.p.) protects against LPS-induced learning/memory decrements in mice. has not independently confirmed the accuracy of these methods. They are for refere

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[1]. Chambers MS, et al. An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties. J Med Chem. 2004 Nov 18;47(24):5829-32.
[2]. Atack JR, 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.

In Vitro: DMSO : 50 mg/mL (135.73 mM; Need ultrasonic)配制储备液