Naloxone HCl | MOR inverse agonist | CAS#357-08-4

MedKoo Cat#: 329670 | Name: Naloxone HCl

Description:

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

Naloxone is a μ-opioid receptor (MOR) inverse agonist. Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system (CNS). Its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- (KOR) and δ-opioid receptors (DOR). The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opiate receptor sites within the CNS (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opiates on these receptors without directly producing any effects itself. Naloxone was approved for opioid overdose by the Food and Drug Administration in 1971

Chemical Structure

Naloxone HCl

CAS#357-08-4 (HCl)

Theoretical Analysis

MedKoo Cat#: 329670

Name: Naloxone HCl

CAS#: 357-08-4 (HCl)

Chemical Formula: C19H22ClNO4

Exact Mass: 0.0000

Molecular Weight: 363.84

Elemental Analysis: C, 62.72; H, 6.10; Cl, 9.74; N, 3.85; O, 17.59

Price and Availability

Size	Price	Availability
50mg	USD 90.00	Ready to ship
100mg	USD 150.00	Ready to Ship
200mg	USD 250.00	Ready to ship

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Related CAS #

465-65-6 (free base) 51481-60-8 (HCl hydrate) 357-08-4 (HCl)

Synonym

Naloxone HCl; EN-15304; EN15304; EN 15304; NIH7890; Naloxone hydrochloride; Narcan; Narcanti; Nalonee;

IUPAC/Chemical Name

(4R,4aS,7aR,12bS)-3-allyl-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one hydrochloride

InChi Key

RGPDIGOSVORSAK-STHHAXOLSA-N

InChi Code

InChI=1S/C19H21NO4.ClH/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11;/h2-4,14,17,21,23H,1,5-10H2;1H/t14-,17+,18+,19-;/m1./s1

SMILES Code

O=C1[C@@](OC2=C(O)C=CC3=C24)([H])[C@@]54CCN(CC=C)[C@@](C3)([H])[C@]5(O)CC1.[H]Cl

Appearance

Solid powder

Purity

>99% (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

Naloxone was patented in 1961 and approved for opioid overdose by the Food and Drug Administration in 1971. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Naloxone is available as a generic medication. Its wholesale price in the developing world is between US$0.50 and 5.30 per dose. The vials of medication are not very expensive (less than 25 USD) in the United States. The price for a package of two auto-injectors in the US, however, has increased from $690 in 2014 to $4,500 in 2016. The Ki affinity values of (−)-naloxone for the MOR, KOR, and DOR have been reported as 0.559 nM, 4.91 nM, and 36.5 nM, respectively, whereas for (+)-naloxone, 3,550 nM, 8,950 nM, and 122,000 nM, respectively, have been reported. As such, (−)-naloxone appears to be the active isomer. Moreover, these data suggest that naloxone binds to the MOR with approximately 9-fold greater affinity relative to the KOR and around 60-fold greater affinity relative to the DOR.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A8T09K21

QC Data

View QC data: current batch, Lot#A8T09K21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Naloxone HCl is an opioid inverse agonist drug used to counter the effects of opiate overdose.

In vitro activity:

The results showed that morphine directly enhanced microglia chemotaxis and membrane ruffling and that these actions were accompanied by an increase in Iba1 protein expression in the microglia, especially in the ruffling membrane. Pretreatment with 1nM (+)-naloxone significantly inhibited microglia migration, activation, and reduced Iba1 expression in microglia. On the basis of these results, Iba1 is involved in microglia migration and that ultralow dose (+)-naloxone may regulate actin cytoskeleton dynamics. Reference: J Formos Med Assoc. 2015 May;114(5):446-55. https://pubmed.ncbi.nlm.nih.gov/25649471/

In vivo activity:

The addition of naloxone at 1.0 or 2.0 µM significantly inhibited the LPS-induced production of TNFα and IL-1β (P < 0.01 for all comparisons). The lowest concentration of naloxone (0.5 µM) significantly inhibited IL-1β (P < 0.05), but not TNF-α production. Western blotting showed that p38 MAPK, JNK and ERK were constitutively present in microglia (Fig. 2A). LPS treatment induced a visible increase in the amount of P-p38 MAPK, but p38 MAPK, JNK, P-JNK, ERK and P-ERK appeared unchanged. Pretreatment with naloxone dose-dependently reversed the LPS-induced increase in P-p38 MAPK (P < 0.05, Fig. 2B). Naloxone had no significant effect on the levels of P-JNK or P-ERK (Fig. 2B). Immunofluoresence microscopy showed weak P-p38 MAPK immunostaining in OX42-positive rat microglial cells in untreated cultures (Fig. 3A). LPS-activation was accompanied by an increase in P-p38 MAPK immunostaining (Fig. 3B). Pretreatment with naloxone (Fig. 3C) resulted in P-p38 MAPK staining similar to that seen in untreated control cultures. Reference: J Int Med Res. 2012;40(4):1438-48. https://pubmed.ncbi.nlm.nih.gov/22971495/

	Solvent	mg/mL	mM
Solubility
	Soluble in DMSO	3.0	8.20

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 363.84 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. Bimonte S, Barbieri A, Cascella M, Rea D, Palma G, Del Vecchio V, Forte CA, Del Prato F, Arra C, Cuomo A. The effects of naloxone on human breast cancer progression: in vitro and in vivo studies on MDA.MB231 cells. Onco Targets Ther. 2018 Jan 3;11:185-191. doi: 10.2147/OTT.S145780. PMID: 29379300; PMCID: PMC5757202. 2. Tsai RY, Cheng YC, Wong CS. (+)-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia. J Formos Med Assoc. 2015 May;114(5):446-55. doi: 10.1016/j.jfma.2014.12.004. Epub 2015 Jan 31. PMID: 25649471. 3. Bimonte S, Barbieri A, Cascella M, Rea D, Palma G, Luciano A, Forte CA, Cuomo A, Arra C. Naloxone Counteracts the Promoting Tumor Growth Effects Induced by Morphine in an Animal Model of Triple-negative Breast Cancer. In Vivo. 2019 May-Jun;33(3):821-825. doi: 10.21873/invivo.11545. PMID: 31028203; PMCID: PMC6559888. 4. Xu YF, Fu LL, Jiang CH, Qin YW, Ni YQ, Fan JW. Naloxone inhibition of lipopolysaccharide-induced activation of retinal microglia is partly mediated via the p38 mitogen activated protein kinase signalling pathway. J Int Med Res. 2012;40(4):1438-48. doi: 10.1177/147323001204000422. PMID: 22971495.

In vitro protocol:

In vivo protocol:

1. Bimonte S, Barbieri A, Cascella M, Rea D, Palma G, Luciano A, Forte CA, Cuomo A, Arra C. Naloxone Counteracts the Promoting Tumor Growth Effects Induced by Morphine in an Animal Model of Triple-negative Breast Cancer. In Vivo. 2019 May-Jun;33(3):821-825. doi: 10.21873/invivo.11545. PMID: 31028203; PMCID: PMC6559888. 2. Xu YF, Fu LL, Jiang CH, Qin YW, Ni YQ, Fan JW. Naloxone inhibition of lipopolysaccharide-induced activation of retinal microglia is partly mediated via the p38 mitogen activated protein kinase signalling pathway. J Int Med Res. 2012;40(4):1438-48. doi: 10.1177/147323001204000422. PMID: 22971495.

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