Mrk 016

Manufactured by Bio-Techne

The MRK-016 is a lab equipment product from Bio-Techne. It is designed for use in scientific research and laboratory settings. The core function of this product is to facilitate specific tasks or processes required in the course of research activities. No further details about the intended use or features of this product can be provided in an unbiased and factual manner.

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Lab products found in correlation

Ketamine hydrochloride, by Merck Group (1 mentions) Flumazenil, by Bio-Techne (1 mentions)

2 protocols using mrk 016

Intranasal Ketamine and MRK-016 Effects

Cited 1 time

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Ketamine-hydrochloride (Sigma-Aldrich), MRK-016 (Tocris), and fluoxetine hydrochloride (FLX; National Institute of Mental Health Chemical Synthesis and Drug Supply Program) were dissolved in DMSO and administered intraperitoneally in a volume of 1.125 ml/kg of body mass. 2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX; National Institute of Mental Health Chemical Synthesis and Drug Supply Program) was dissolved in 0.9% saline and administered intraperitoneally in a volume of 7.5 ml/kg of body mass. Ketamine was administered at 10 mg/kg, a widely used sub-anesthetic dose widely used in rodent studies to induce antidepressant effects (Maeng et al., 2008 (link); Zanos et al., 2016 (link)). Unless stated otherwise, MRK-016 was administered at 3 mg/kg, a dose chosen to produce 70% receptor occupancy (Atack et al., 2009 (link)). MRK-016 has equivalent affinity for α1-, α2-, α3-, and α5-containing GABA_ARs but has a 5- to 10-fold greater efficacy at inhibiting GABA_ARs containing α5 subunits (Atack et al., 2009).

Zanos P., Nelson M.E., Highland J.N., Krimmel S.R., Georgiou P., Gould T.D, & Thompson S.M. (2017). A Negative Allosteric Modulator for α5 Subunit-Containing GABA Receptors Exerts a Rapid and Persistent Antidepressant-Like Action without the Side Effects of the NMDA Receptor Antagonist Ketamine in Mice. eNeuro, 4(1), ENEURO.0285-16.2017.

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Pharmacological Modulation of Benzodiazepine Receptors

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MRK-016 (Tocris Bioscience, R&D Systems, Minneapolis, MN) was prepared in 100% DMSO and injected at 3mg/kg intraperitoneally (i.p.), a dose shown to produce 85% receptor occupancy in rats³¹ (injection volume = 40-50 μL). Flumazenil (Tocris Bioscience) was prepared in 100% DMSO and injected at 20mg/kg. This dose was calculated to be sufficient to antagonize the benzodiazepine site based on half-life in the rodent brain and its ability to restore the benzodiazepine-induced loss of righting-reflex in mice³⁵ for the duration of MRK-016’s rodent elimination half-life³¹. (R,S) ketamine was purchased from Sigma-Aldrich, prepared in 0.9% saline and injected at 10mg/kg i.p. (100-150 μL).

Troppoli T.A., Zanos P., Georgiou P., Gould T.D., Rudolph U, & Thompson S.M. (2021). Negative allosteric modulation of GABAARs at α5 subunit-containing benzodiazepine sites reverses stress-induced anhedonia and weakened synaptic function in mice. Biological psychiatry, 92(3), 216-226.

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