Ro 25-6981 maleate | CAS#1312991-76-6 | 169274-78-6 | NR2B/NMDA antagonist

MedKoo Cat#: 526651 | Name: Ro 25-6981 maleate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ro 25-6981 is a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit.

Chemical Structure

Ro 25-6981 maleate

CAS#1312991-76-6 (maleate)

Theoretical Analysis

MedKoo Cat#: 526651

Name: Ro 25-6981 maleate

CAS#: 1312991-76-6 (maleate)

Chemical Formula: C26H33NO6

Exact Mass: 0.0000

Molecular Weight: 455.55

Elemental Analysis: C, 68.55; H, 7.30; N, 3.07; O, 21.07

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 350.00	2 Weeks
10mg	USD 550.00	2 Weeks

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Related CAS #

169274-78-6 (free base) 1312991-76-6 (maleate) 919289-58-0 (HCl)

Synonym

Ro 25-6981; Ro25-6981; Ro-25-6981; Ro-256981; Ro 256981; Ro256981; Ro 25-6981 maleate

IUPAC/Chemical Name

4-((1R,2S)-3-(4-benzylpiperidin-1-yl)-1-hydroxy-2-methylpropyl)phenol maleate

InChi Key

FYJZEHCQSUBZDY-SEELMCCHSA-N

InChi Code

InChI=1S/C22H29NO2.C4H4O4/c1-17(22(25)20-7-9-21(24)10-8-20)16-23-13-11-19(12-14-23)15-18-5-3-2-4-6-18;5-3(6)1-2-4(7)8/h2-10,17,19,22,24-25H,11-16H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t17-,22+;/m0./s1

SMILES Code

OC1=CC=C([C@H](O)[C@@H](C)CN2CCC(CC3=CC=CC=C3)CC2)C=C1.O=C(O)/C=C\C(O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Ro 25-6981 inhibited 3H-MK-801 binding to rat forebrain membranes in a biphasic manner with IC50 values of 0.003 microM and 149 microM for high- (about 60%) and low-affinity sites, respectively. NMDA receptor subtypes expressed in Xenopus oocytes were blocked with IC50 values of 0.009 microM and 52 microM for the subunit combinations NR1C & NR2B and NR1C & NR2A, respectively, which indicated a >5000-fold selectivity.

In vitro activity:

Ro 25-6981 is a highly selective, activity-dependent blocker of NMDA receptors that contain the NR2B subunit. Ro 25-6981 blocked NMDA receptor subtypes in an activity-dependent manner. Ro 25-6981 protected cultured cortical neurons against glutamate toxicity and combined oxygen and glucose deprivation with IC50 values of 0.4 microM and 0.04 microM, respectively. Reference: J Pharmacol Exp Ther. 1997 Dec;283(3):1285-92. https://pubmed.ncbi.nlm.nih.gov/9400004/

In vivo activity:

Ro 25-6981 was effective against PTZ-induced seizures in infantile rats, specifically suppressing the tonic phase of the generalized tonic-clonic seizures, but it failed in juveniles. Neither sensorimotor development nor cognitive abilities and emotionality were affected by early-life exposure to Ro 25-6981. Reference: Pharmaceutics. 2021 Sep 16;13(9):1482. https://pubmed.ncbi.nlm.nih.gov/34575558/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	219.52
	Water	8.3	18.29

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 455.55 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Mutel V, Buchy D, Klingelschmidt A, Messer J, Bleuel Z, Kemp JA, Richards JG. In vitro binding properties in rat brain of [3H]Ro 25-6981, a potent and selective antagonist of NMDA receptors containing NR2B subunits. J Neurochem. 1998 May;70(5):2147-55. doi: 10.1046/j.1471-4159.1998.70052147.x. PMID: 9572302. 2. Fischer G, Mutel V, Trube G, Malherbe P, Kew JN, Mohacsi E, Heitz MP, Kemp JA. Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther. 1997 Dec;283(3):1285-92. PMID: 9400004. 3. Mareš P, Kozlová L, Mikulecká A, Kubová H. The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats. Pharmaceutics. 2021 Sep 16;13(9):1482. doi: 10.3390/pharmaceutics13091482. PMID: 34575558; PMCID: PMC8469742. 4. Szczurowska E, Mareš P. Different action of a specific NR2B/NMDA antagonist Ro 25-6981 on cortical evoked potentials and epileptic afterdischarges in immature rats. Brain Res Bull. 2015 Feb;111:1-8. doi: 10.1016/j.brainresbull.2014.11.001. Epub 2014 Nov 11. PMID: 25446739.

In vitro protocol:

In vivo protocol:

1. Mareš P, Kozlová L, Mikulecká A, Kubová H. The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats. Pharmaceutics. 2021 Sep 16;13(9):1482. doi: 10.3390/pharmaceutics13091482. PMID: 34575558; PMCID: PMC8469742. 2. Szczurowska E, Mareš P. Different action of a specific NR2B/NMDA antagonist Ro 25-6981 on cortical evoked potentials and epileptic after discharges in immature rats. Brain Res Bull. 2015 Feb;111:1-8. doi: 10.1016/j.brainresbull.2014.11.001. Epub 2014 Nov 11. PMID: 25446739.

1: Nasarudeen R, Singh A, Rana ZS, Punnakkal P. Epileptiform activity induced metaplasticity impairs bidirectional plasticity in the hippocampal CA1 synapses via GluN2B NMDA receptors. Exp Brain Res. 2022 Dec;240(12):3339-3349. doi: 10.1007/s00221-022-06486-5. Epub 2022 Nov 7. PMID: 36344756. 2: Li A, Huang CJ, Gu KP, Huang Y, Huang YQ, Zhang H, Lin JP, Liu YF, Yang Y, Yao YX. PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B. Sci Rep. 2022 Oct 12;12(1):17114. doi: 10.1038/s41598-022-21488-7. PMID: 36224339; PMCID: PMC9556829. 3: Pochwat B, Misztak P, Masternak J, Bączyńska E, Bijata K, Roszkowska M, Bijata M, Włodarczyk J, Szafarz M, Wyska E, Muszyńska B, Krakowska A, Opoka W, Nowak G, Szewczyk B. Combined hyperforin and lanicemine treatment instead of ketamine or imipramine restores behavioral deficits induced by chronic restraint stress and dietary zinc restriction in mice. Front Pharmacol. 2022 Aug 24;13:933364. doi: 10.3389/fphar.2022.933364. PMID: 36091748; PMCID: PMC9448861. 4: Lee JR, Jeong KW. NMDA Receptor Antagonists Degrade Lipofuscin via Autophagy in Human Retinal Pigment Epithelial Cells. Medicina (Kaunas). 2022 Aug 20;58(8):1129. doi: 10.3390/medicina58081129. PMID: 36013596; PMCID: PMC9415004. 5: Shipton OA, Tang CS, Paulsen O, Vargas-Caballero M. Differential vulnerability of hippocampal CA3-CA1 synapses to Aβ. Acta Neuropathol Commun. 2022 Apr 4;10(1):45. doi: 10.1186/s40478-022-01350-7. PMID: 35379353; PMCID: PMC8981624. 6: Matt L, Pham T, Skrabak D, Hoffmann F, Eckert P, Yin J, Gisevius M, Ehinger R, Bausch A, Ueffing M, Boldt K, Ruth P, Lukowski R. The Na+-activated K+ channel Slack contributes to synaptic development and plasticity. Cell Mol Life Sci. 2021 Dec;78(23):7569-7587. doi: 10.1007/s00018-021-03953-0. Epub 2021 Oct 18. PMID: 34664085; PMCID: PMC8629810. 7: Mareš P, Kozlová L, Mikulecká A, Kubová H. The GluN2B-Selective Antagonist Ro 25-6981 Is Effective against PTZ-Induced Seizures and Safe for Further Development in Infantile Rats. Pharmaceutics. 2021 Sep 16;13(9):1482. doi: 10.3390/pharmaceutics13091482. PMID: 34575558; PMCID: PMC8469742. 8: Licheri V, Chandrasekaran J, Bird CW, Valenzuela CF, Brigman JL. Sex-specific effect of prenatal alcohol exposure on N-methyl-D-aspartate receptor function in orbitofrontal cortex pyramidal neurons of mice. Alcohol Clin Exp Res. 2021 Oct;45(10):1994-2005. doi: 10.1111/acer.14697. Epub 2021 Sep 29. PMID: 34523139; PMCID: PMC8602746. 9: Gakare SG, Varghese SS, Patni PP, Wagh SA, Ugale RR. Prevention of glutamate excitotoxicity in lateral habenula alleviates ethanol withdrawal-induced somatic and behavioral effects in ethanol dependent mice. Behav Brain Res. 2022 Jan 7;416:113557. doi: 10.1016/j.bbr.2021.113557. Epub 2021 Aug 25. PMID: 34453973. 10: Ahnaou A, Heleven K, Biermans R, Manyakov NV, Drinkenburg WH. NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats. Int J Mol Sci. 2021 Aug 12;22(16):8672. doi: 10.3390/ijms22168672. PMID: 34445376; PMCID: PMC8395520. 11: Pascual-Antón R, Blasco-Serra A, Muñoz-Moreno E, Pilar-Cuéllar F, Garro- Martínez E, Florensa-Zanuy E, López-Gil X, Campa VM, Soria G, Adell A. Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study. Brain Struct Funct. 2021 Nov;226(8):2603-2616. doi: 10.1007/s00429-021-02354-0. Epub 2021 Aug 7. PMID: 34363521; PMCID: PMC8448713. 12: Wang C, Yu Q, Li D, Sun N, Huang Y, Zhang YX, Zhou WX. Reduced D-Serine Release May Contribute to Impairment of Long-Term Potentiation by Corticosterone in the Perforant Path-Dentate Gyrus. Neurochem Res. 2021 Sep;46(9):2359-2375. doi: 10.1007/s11064-021-03380-4. Epub 2021 Jun 19. PMID: 34146194. 13: She X, Gao Y, Zhao Y, Yin Y, Dong Z. A high-throughput screen identifies inhibitors of lung cancer stem cells. Biomed Pharmacother. 2021 Aug;140:111748. doi: 10.1016/j.biopha.2021.111748. Epub 2021 May 25. PMID: 34044271. 14: Wang YW, Zhang YY, Wu ZY, Cheng ED, Chen YQ, Shen W, Zhang LC, Zhang SM. GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats. Sheng Li Xue Bao. 2021 Apr 25;73(2):223-232. PMID: 33903884. 15: Xiao Y, Xie L, Xu QY, Chen L, Chen H, Xu GY, Zhang PA. Transcranial direct current stimulation relieves visceral hypersensitivity via normalizing GluN2B expression and neural activity in anterior cingulate cortex. J Neurophysiol. 2021 May 1;125(5):1787-1797. doi: 10.1152/jn.00025.2021. Epub 2021 Mar 24. PMID: 33760644; PMCID: PMC8356761. 16: Heaney CF, Namjoshi SV, Uneri A, Bach EC, Weiner JL, Raab-Graham KF. Role of FMRP in rapid antidepressant effects and synapse regulation. Mol Psychiatry. 2021 Jun;26(6):2350-2362. doi: 10.1038/s41380-020-00977-z. Epub 2021 Jan 12. PMID: 33432187; PMCID: PMC8440195. 17: Liu Y, Wang Z, Zhang X, Li S, Wu W, Li X, Yang Y. A sex-dependent delayed maturation of visual plasticity induced by adverse experiences in early childhood. Neurobiol Stress. 2020 Oct 14;13:100256. doi: 10.1016/j.ynstr.2020.100256. PMID: 33344711; PMCID: PMC7739182. 18: Westbrook SR, Gulley JM. Effects of the GluN2B antagonist, Ro 25-6981, on extinction consolidation following adolescent- or adult-onset methamphetamine self-administration in male and female rats. Behav Pharmacol. 2020 Dec;31(8):748-758. doi: 10.1097/FBP.0000000000000586. PMID: 32925228. 19: Pochwat B, Domin H, Rafało-Ulińska A, Szewczyk B, Nowak G. Ketamine and Ro 25-6981 Reverse Behavioral Abnormalities in Rats Subjected to Dietary Zinc Restriction. Int J Mol Sci. 2020 Jul 6;21(13):4791. doi: 10.3390/ijms21134791. PMID: 32640759; PMCID: PMC7369754. 20: Nishitani A, Nagayoshi H, Takenaka S, Asano M, Shimizu S, Ohno Y, Kuramoto T. Involvement of NMDA receptors in tremor expression in Aspa/Hcn1 double- knockout rats. Exp Anim. 2020 Nov 12;69(4):388-394. doi: 10.1538/expanim.20-0025. Epub 2020 Jun 5. PMID: 32507787; PMCID: PMC7677080.