Ro64-6198 | CAS#280783-56-4 |NOP agonist

MedKoo Cat#: 532569 | Name: Ro64-6198

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Description:

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

Ro64-6198 is a nociceptin/orphanin FQ receptor (NOP) agonist which impairs mnemonic function through glutamatergic-dependent mechanisms.

Chemical Structure

Ro64-6198

CAS#280783-56-4

Theoretical Analysis

MedKoo Cat#: 532569

Name: Ro64-6198

CAS#: 280783-56-4

Chemical Formula: C26H31N3O

Exact Mass: 401.2467

Molecular Weight: 401.55

Elemental Analysis: C, 77.77; H, 7.78; N, 10.46; O, 3.98

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00
25mg	USD 1,000.00

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Related CAS #

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Synonym

Ro64-6198; Ro 64-6198; Ro-64-6198.

IUPAC/Chemical Name

8-[(1S,3aS)-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one

InChi Key

JLFMYEAXZNPWBK-REWPJTCUSA-N

InChi Code

InChI=1S/C26H31N3O/c30-25-26(29(18-27-25)21-9-2-1-3-10-21)14-16-28(17-15-26)23-13-12-20-7-4-6-19-8-5-11-22(23)24(19)20/h1-3,5,8-11,20,23H,4,6-7,12-18H2,(H,27,30)/t20-,23-/m0/s1

SMILES Code

O=C1NCN(C2=CC=CC=C2)C13CCN([C@H]4CC[C@]5([H])CCCC6=CC=CC4=C56)CC3

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

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 64-6198 is a brain-penetrant, nonpeptidic, high-affinity (Ki = 0.389 nM against 0.1 nM OFQ for binding human ORL1) nociceptin/orphanin FQ (N/OFQ) receptor ORL-1 (KOR-3, NOP) agonist (EC50 = 38.9 nM by GTPγS binding assay; IC50 = 32.4 nM against forskolin-stimulated cellular cAMP accumulation) with >100-fold selectivity over other opioid receptor family members (Ki = 46.8 nM/μ, 89.1 nM/k, 1.38 μM/δ) and no significant affinity toward 48 other receptors and ion channels (IC50 >1 μM).

In vitro activity:

This study characterizes the pharmacodynamics of Ro 64-6198 in cAMP and G-protein coupling in vitro and examine. For the first time, the effects of NPO FQ and Ro 64-6198 in arrestin recruitment assays. Reference: ACS Chem Neurosci. 2015 Dec 16;6(12):1956-64. https://pubmed.ncbi.nlm.nih.gov/26367173/

In vivo activity:

This study suggests that NOP receptor agonists, one being Ro 64-6198, should be explored as treatment for migraine symptoms. In mice, Ro 64-6198 dose dependently blocked nitroglycerin-induced paw and head allodynia. Ro 64-6198 can decrease nitroglycerin-induced light sensitivity in mice. Reference: Neuropharmacology. 2020 Jun 15;170:108029. https://pubmed.ncbi.nlm.nih.gov/32278976/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	124.52

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 401.55 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. Chang SD, Brieaddy LE, Harvey JD, Lewin AH, Mascarella SW, Seltzman HH, Reddy PA, Decker AM, McElhinny CJ Jr, Zhong D, Peterson EE, Navarro HA, Bruchas MR, Carroll FI. Novel Synthesis and Pharmacological Characterization of NOP Receptor Agonist 8-[(1S,3aS)-2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (Ro 64-6198). ACS Chem Neurosci. 2015 Dec 16;6(12):1956-64. doi: 10.1021/acschemneuro.5b00208. Epub 2015 Sep 30. PMID: 26367173; PMCID: PMC5572205. 2. Targowska-Duda KM, Ozawa A, Bertels Z, Cippitelli A, Marcus JL, Mielke-Maday HK, Zribi G, Rainey AN, Kieffer BL, Pradhan AA, Toll L. NOP receptor agonist attenuates nitroglycerin-induced migraine-like symptoms in mice. Neuropharmacology. 2020 Jun 15;170:108029. doi: 10.1016/j.neuropharm.2020.108029. Epub 2020 Mar 6. PMID: 32278976; PMCID: PMC7243257. 3. Cornelissen JC, Steele FF, Tenney RD, Obeng S, Rice KC, Zhang Y, Banks ML. Role of mu-opioid agonist efficacy on antinociceptive interactions between mu agonists and the nociceptin opioid peptide agonist Ro 64-6198 in rhesus monkeys. Eur J Pharmacol. 2019 Feb 5;844:175-182. doi: 10.1016/j.ejphar.2018.12.021. Epub 2018 Dec 12. PMID: 30552903; PMCID: PMC6445635.

In vitro protocol:

In vivo protocol:

1. Targowska-Duda KM, Ozawa A, Bertels Z, Cippitelli A, Marcus JL, Mielke-Maday HK, Zribi G, Rainey AN, Kieffer BL, Pradhan AA, Toll L. NOP receptor agonist attenuates nitroglycerin-induced migraine-like symptoms in mice. Neuropharmacology. 2020 Jun 15;170:108029. doi: 10.1016/j.neuropharm.2020.108029. Epub 2020 Mar 6. PMID: 32278976; PMCID: PMC7243257. 2. Cornelissen JC, Steele FF, Tenney RD, Obeng S, Rice KC, Zhang Y, Banks ML. Role of mu-opioid agonist efficacy on antinociceptive interactions between mu agonists and the nociceptin opioid peptide agonist Ro 64-6198 in rhesus monkeys. Eur J Pharmacol. 2019 Feb 5;844:175-182. doi: 10.1016/j.ejphar.2018.12.021. Epub 2018 Dec 12. PMID: 30552903; PMCID: PMC6445635.

1: Morairty SR, Sun Y, Toll L, Bruchas MR, Kilduff TS. Activation of the nociceptin/orphanin-FQ receptor promotes NREM sleep and EEG slow wave activity. Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2214171120. doi: 10.1073/pnas.2214171120. Epub 2023 Mar 22. PMID: 36947514; PMCID: PMC10068791. 2: Walentiny DM, Wiebelhaus JM, Beardsley PM. Nociceptin/orphanin FQ receptors modulate the discriminative stimulus effects of oxycodone in C57BL/6 mice. Drug Alcohol Depend. 2018 Jun 1;187:335-342. doi: 10.1016/j.drugalcdep.2018.02.035. Epub 2018 Apr 15. PMID: 29705547. 3: Reiss D, Prinssen EP, Wichmann J, Kieffer BL, Ouagazzal AM. The nociceptin orphanin FQ peptide receptor agonist, Ro64-6198, impairs recognition memory formation through interaction with glutamatergic but not cholinergic receptor antagonists. Neurobiol Learn Mem. 2012 Oct;98(3):254-60. doi: 10.1016/j.nlm.2012.09.002. Epub 2012 Sep 13. PMID: 22982481. 4: Ces A, Reiss D, Walter O, Wichmann J, Prinssen EP, Kieffer BL, Ouagazzal AM. Activation of nociceptin/orphanin FQ peptide receptors disrupts visual but not auditory sensorimotor gating in BALB/cByJ mice: comparison to dopamine receptor agonists. Neuropsychopharmacology. 2012 Jan;37(2):378-89. doi: 10.1038/npp.2011.175. Epub 2011 Aug 31. PMID: 21881568; PMCID: PMC3242299. 5: Rutten K, De Vry J, Bruckmann W, Tzschentke TM. Effects of the NOP receptor agonist Ro65-6570 on the acquisition of opiate- and psychostimulant-induced conditioned place preference in rats. Eur J Pharmacol. 2010 Oct 25;645(1-3):119-26. doi: 10.1016/j.ejphar.2010.07.036. Epub 2010 Jul 30. PMID: 20674566. 6: Goeldner C, Reiss D, Wichmann J, Kieffer BL, Ouagazzal AM. Activation of nociceptin opioid peptide (NOP) receptor impairs contextual fear learning in mice through glutamatergic mechanisms. Neurobiol Learn Mem. 2009 May;91(4):393-401. doi: 10.1016/j.nlm.2008.12.001. Epub 2009 Jan 22. PMID: 19100850; PMCID: PMC4482120. 7: Goeldner C, Reiss D, Wichmann J, Meziane H, Kieffer BL, Ouagazzal AM. Nociceptin receptor impairs recognition memory via interaction with NMDA receptor-dependent mitogen-activated protein kinase/extracellular signal- regulated kinase signaling in the hippocampus. J Neurosci. 2008 Feb 27;28(9):2190-8. doi: 10.1523/JNEUROSCI.3711-07.2008. PMID: 18305252; PMCID: PMC6671849. 8: Reiss D, Wichmann J, Tekeshima H, Kieffer BL, Ouagazzal AM. Effects of nociceptin/orphanin FQ receptor (NOP) agonist, Ro64-6198, on reactivity to acute pain in mice: comparison to morphine. Eur J Pharmacol. 2008 Jan 28;579(1-3):141-8. doi: 10.1016/j.ejphar.2007.10.031. Epub 2007 Oct 25. PMID: 18031727. 9: Gehlert DR, Gackenheimer SL, Shaw JL. Distribution of nociceptin and Ro64-6198 activated [35S]-GTPgammaS binding in the rat brain. Neuropeptides. 2006 Apr;40(2):95-105. doi: 10.1016/j.npep.2005.11.002. Epub 2006 Jan 3. PMID: 16403422. 10: Varty GB, Hyde LA, Hodgson RA, Lu SX, McCool MF, Kazdoba TM, Del Vecchio RA, Guthrie DH, Pond AJ, Grzelak ME, Xu X, Korfmacher WA, Tulshian D, Parker EM, Higgins GA. Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species. Psychopharmacology (Berl). 2005 Oct;182(1):132-43. doi: 10.1007/s00213-005-0041-4. Epub 2005 Sep 29. PMID: 16025321. 11: Obara I, Przewlocki R, Przewlocka B. Spinal and local peripheral antiallodynic activity of Ro64-6198 in neuropathic pain in the rat. Pain. 2005 Jul;116(1-2):17-25. doi: 10.1016/j.pain.2005.03.012. PMID: 15927383. 12: Corbani M, Gonindard C, Meunier JC. Ligand-regulated internalization of the opioid receptor-like 1: a confocal study. Endocrinology. 2004 Jun;145(6):2876-85. doi: 10.1210/en.2004-0062. Epub 2004 Mar 11. PMID: 15016723. 13: McDonald J, Calo G, Guerrini R, Lambert DG. UFP-101, a high affinity antagonist for the nociceptin/orphanin FQ receptor: radioligand and GTPgamma(35)S binding studies. Naunyn Schmiedebergs Arch Pharmacol. 2003 Feb;367(2):183-7. doi: 10.1007/s00210-002-0661-8. Epub 2003 Jan 15. PMID: 12595960. 14: Hashiba E, Lambert DG, Jenck F, Wichmann J, Smith G. Characterisation of the non-peptide nociceptin receptor agonist, Ro64-6198 in Chinese hamster ovary cells expressing recombinant human nociceptin receptors. Life Sci. 2002 Mar 1;70(15):1719-25. doi: 10.1016/s0024-3205(02)01477-7. PMID: 12002517. 15: Higgins GA, Grottick AJ, Ballard TM, Richards JG, Messer J, Takeshima H, Pauly-Evers M, Jenck F, Adam G, Wichmann J. Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function. Neuropharmacology. 2001 Jul;41(1):97-107. doi: 10.1016/s0028-3908(01)00048-x. PMID: 11445190.