U-69593 | CAS#96744-75-1 | opioid receptor agonist

MedKoo Cat#: 527820 | Name: U-69593

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Description:

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

U-69593 is a potent and selective κ₁-opioid receptor agonist, known for its analgesic, anti-inflammatory, and anxiolytic properties. It has been shown to produce antinociception, reduce inflammation, and alleviate anxiety in animal models. Additionally, U-69593 has been observed to inhibit the peripheral secretion of oxytocin and vasopressin in rats, while having minimal effect on gastrointestinal motility.

Chemical Structure

U-69593

CAS#96744-75-1 (free base)

Theoretical Analysis

MedKoo Cat#: 527820

Name: U-69593

CAS#: 96744-75-1 (free base)

Chemical Formula: C22H32N2O2

Exact Mass: 356.2464

Molecular Weight: 356.51

Elemental Analysis: C, 74.12; H, 9.05; N, 7.86; O, 8.98

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00	2 Weeks
25mg	USD 1,250.00	2 Weeks

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Related CAS #

1313288-99-1 (free base) 96744-75-1 (free base) U69593 HCl U-69593 Maleate

Synonym

U069593; U 69593; U-69593

IUPAC/Chemical Name

(+)-N-methyl-2-phenyl-N-[(5R,7S,8S)-7-pyrrolidin-1-yl-1-oxaspiro[4.5]decan-8-yl]acetamide

InChi Key

PGZRDDYTKFZSFR-ONTIZHBOSA-N

InChi Code

InChI=1S/C22H32N2O2/c1-23(21(25)16-18-8-3-2-4-9-18)19-10-12-22(11-7-15-26-22)17-20(19)24-13-5-6-14-24/h2-4,8-9,19-20H,5-7,10-17H2,1H3/t19-,20-,22-/m0/s1

SMILES Code

O=C(N(C)[C@@H](CC1)[C@@H](N2CCCC2)C[C@@]31CCCO3)CC4=CC=CC=C4

Appearance

Solid powder

Purity

>95 % (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

Certificate of Analysis

View CoA: current batch, Lot#C25M01C14

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

κ Opioid Receptor/KOR

In vitro activity:

Fentanyl and U69593 reduced electrically induced contractions, whereas morphine reduced them only slightly. Naloxone competitively antagonised U69593, but both naloxone and naloxonazine were unable to counteract the inhibition of contractions induced by fentanyl. The inhibition of contractions shown by fentanyl is therefore probably not mediated by opioid receptors, but due to an anticholinergic activity of this drug. Reference: Menozzi A, Pozzoli C, Zullian C, Poli E, Serventi P, Bertini S. Inhibition of motility in isolated horse small intestine is mediated by κ but not µ opioid receptors. Equine Vet J. 2012 May;44(3):368-70. doi: 10.1111/j.2042-3306.2011.00426.x. Epub 2011 Aug 23. PMID: 21883413.

In vivo activity:

Rats were injected once daily with the selective KOR agonist U-69593 or vehicle for four consecutive days. One-day after the last U-69593 injection, microdialysis studies assessing extracellular DA levels in the NAc and locomotor activity challenged with amphetamine were conducted. Microdialysis studies revealed that preexposure to U-69593 had no effect on basal DA levels but significantly augmented amphetamine-induced DA extracellular levels. Reference: Fuentealba JA, Gysling K, Andrés ME. Increased locomotor response to amphetamine induced by the repeated administration of the selective kappa-opioid receptor agonist U-69593. Synapse. 2007 Sep;61(9):771-7. doi: 10.1002/syn.20424. PMID: 17568430.

	Solvent	mg/mL	mM
Solubility
	DMF	10.0	28.45

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 356.51 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:

In vitro protocol:

1. Menozzi A, Pozzoli C, Zullian C, Poli E, Serventi P, Bertini S. Inhibition of motility in isolated horse small intestine is mediated by κ but not µ opioid receptors. Equine Vet J. 2012 May;44(3):368-70. doi: 10.1111/j.2042-3306.2011.00426.x. Epub 2011 Aug 23. PMID: 21883413. 2. Kuo A, Magiera J, Rethwan N, Andersson Å, Leen Lam A, Wyse B, Meutermans W, Lewis R, Smith M. In vitro profiling of opioid ligands using the cAMP formation inhibition assay and the β-arrestin2 recruitment assay: No two ligands have the same profile. Eur J Pharmacol. 2020 Apr 5;872:172947. doi: 10.1016/j.ejphar.2020.172947. Epub 2020 Jan 25. PMID: 31991138.

In vivo protocol:

1. Fuentealba JA, Gysling K, Andrés ME. Increased locomotor response to amphetamine induced by the repeated administration of the selective kappa-opioid receptor agonist U-69593. Synapse. 2007 Sep;61(9):771-7. doi: 10.1002/syn.20424. PMID: 17568430. 2. Fuentealba JA, Gysling K, Magendzo K, Andrés ME. Repeated administration of the selective kappa-opioid receptor agonist U-69593 increases stimulated dopamine extracellular levels in the rat nucleus accumbens. J Neurosci Res. 2006 Aug 1;84(2):450-9. doi: 10.1002/jnr.20890. PMID: 16676328.

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Psychopharmacology (Berl). 2015 Sep;232(17):3249-58. doi: 10.1007/s00213-015-3982-2. Epub 2015 Jun 5. PubMed PMID: 26041338; PubMed Central PMCID: PMC4536134. 10: Tejeda HA, Hanks AN, Scott L, Mejias-Aponte C, Hughes ZA, O'Donnell P. Prefrontal Cortical Kappa Opioid Receptors Attenuate Responses to Amygdala Inputs. Neuropsychopharmacology. 2015 Dec;40(13):2856-64. doi: 10.1038/npp.2015.138. Epub 2015 May 14. PubMed PMID: 25971593; PubMed Central PMCID: PMC4864622. 11: Lovell KM, Frankowski KJ, Stahl EL, Slauson SR, Yoo E, Prisinzano TE, Aubé J, Bohn LM. Structure-activity relationship studies of functionally selective kappa opioid receptor agonists that modulate ERK 1/2 phosphorylation while preserving G protein over βarrestin2 signaling bias. ACS Chem Neurosci. 2015 Aug 19;6(8):1411-9. doi: 10.1021/acschemneuro.5b00092. Epub 2015 May 1. Erratum in: ACS Chem Neurosci. 2017 Jul 19;8(7):1628. PubMed PMID: 25891774; PubMed Central PMCID: PMC4830356. 12: Negus SS, Neddenriep B, Altarifi AA, Carroll FI, Leitl MD, Miller LL. Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice. Pain. 2015 Jun;156(6):1153-60. doi: 10.1097/j.pain.0000000000000171. PubMed PMID: 25827812; PubMed Central PMCID: PMC4766843. 13: Guerrieri E, Mallareddy JR, Tóth G, Schmidhammer H, Spetea M. Synthesis and pharmacological evaluation of [(3)H]HS665, a novel, highly selective radioligand for the kappa opioid receptor. ACS Chem Neurosci. 2015 Mar 18;6(3):456-63. doi: 10.1021/cn5002792. Epub 2014 Dec 24. PubMed PMID: 25496417. 14: Arida RM, Gomes da Silva S, de Almeida AA, Cavalheiro EA, Zavala-Tecuapetla C, Brand S, Rocha L. Differential effects of exercise on brain opioid receptor binding and activation in rats. J Neurochem. 2015 Jan;132(2):206-17. doi: 10.1111/jnc.12976. Epub 2014 Nov 17. PubMed PMID: 25330347. 15: Wang ZL, Fang Q, Han ZL, Pan JX, Li XH, Li N, Tang HH, Wang P, Zheng T, Chang XM, Wang R. Opposite effects of neuropeptide FF on central antinociception induced by endomorphin-1 and endomorphin-2 in mice. PLoS One. 2014 Aug 4;9(8):e103773. doi: 10.1371/journal.pone.0103773. eCollection 2014. PubMed PMID: 25090615; PubMed Central PMCID: PMC4121275. 16: Kuo A, Wyse BD, Meutermans W, Smith MT. In vivo profiling of seven common opioids for antinociception, constipation and respiratory depression: no two opioids have the same profile. Br J Pharmacol. 2015 Jan;172(2):532-48. doi: 10.1111/bph.12696. Epub 2014 Jul 1. PubMed PMID: 24641546; PubMed Central PMCID: PMC4292966. 17: Dimattio KM, Yakovleva TV, Aldrich JV, Cowan A, Liu-Chen LY. Zyklophin, a short-acting kappa opioid antagonist, induces scratching in mice. Neurosci Lett. 2014 Mar 20;563:155-9. doi: 10.1016/j.neulet.2014.01.022. Epub 2014 Feb 3. PubMed PMID: 24503508; PubMed Central PMCID: PMC4154496. 18: Gear RW, Bogen O, Ferrari LF, Green PG, Levine JD. NOP receptor mediates anti-analgesia induced by agonist-antagonist opioids. Neuroscience. 2014 Jan 17;257:139-48. doi: 10.1016/j.neuroscience.2013.10.061. Epub 2013 Nov 1. PubMed PMID: 24188792; PubMed Central PMCID: PMC3947912. 19: Gilpin NW, Roberto M, Koob GF, Schweitzer P. Kappa opioid receptor activation decreases inhibitory transmission and antagonizes alcohol effects in rat central amygdala. Neuropharmacology. 2014 Feb;77:294-302. doi: 10.1016/j.neuropharm.2013.10.005. Epub 2013 Oct 21. PubMed PMID: 24157490; PubMed Central PMCID: PMC3873141. 20: Vardy E, Mosier PD, Frankowski KJ, Wu H, Katritch V, Westkaemper RB, Aubé J, Stevens RC, Roth BL. Chemotype-selective modes of action of κ-opioid receptor agonists. J Biol Chem. 2013 Nov 29;288(48):34470-83. doi: 10.1074/jbc.M113.515668. Epub 2013 Oct 11. PubMed PMID: 24121503; PubMed Central PMCID: PMC3843062.