Naloxone

Targets (7)Enzymes (2)Carriers (1)Transporters (2)

Identification

Name

Naloxone

Accession Number

DB01183

Description

Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs, particularly within the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide. More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors. When taken in large quantities, opioid medications such as morphine, hydromorphone, methadone, heroin, or fentanyl are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils. If untreated, this can progress to vomiting, absent pulse and breathing, loss of consciousness, and even death. Naloxone is indicated for the rapid reversal of these symptoms of central nervous system depression in opioid overdose. It's important to note that naloxone only works on opioid receptors within the body, and is therefore not capable of reversing the effects of non-opioid medications such as stimulants like methamphetamine or cocaine, or benzodiazepines like lorazepam or diazepam.

Also known as the brand name product Narcan, naloxone is currently available by intramuscular (IM) or subcutaneous (SubQ) injection, nasal spray, or intravenous (IV) infusion. Naloxone IM injections are commonly available in the form of "kits", which is ideal for making overdose treatment accessible and readily available for administration by minimally trained individuals within the community. Kits commonly include the supplies necessary to treat an overdose in a non-medical setting such as alcohol swabs, syringes, a rescue breathing mask, and instructions for use. Frequently also carried by medical and emergency personnel and at events known to be associated with heavy drug use like music festivals, naloxone kits are considered a key component of harm reduction strategies.

When injected intramuscularly (IM), naloxone acts within 3-5 minutes. Administration of naloxone is associated with very few side effects. Notably, if injected into a person not currently using opioid medications, there would be no noticeable effects at all. However, for individuals using opioid medications or experiencing an overdose, IM injection of naloxone rapidly reverses opioid effects and can cause the injected individual to immediately experience withdrawal symptoms. Common symptoms of opioid withdrawal include nausea, vomiting, sweating, runny nose, aches, and diarrhea. Although certainly physically uncomfortable, opioid withdrawal symptoms are not life-threatening; administration of naloxone is therefore appropriate for any person appearing to have any symptoms of an opioid overdose. Due to its short duration of action, persons injected with naloxone should be monitored for responsiveness and potentially injected a second time or taken to the hospital.

Naloxone is also available within the combination product Suboxone with the opioid medication buprenorphine. Suboxone is used for the maintenance treatment of opioid dependence and addiction. When taken orally, naloxone has no pharmacological effect and does not reduce the effectiveness of the opioid effect of buprenorphine. The primary purpose of including naloxone within Suboxone is to act as a deterrent to injection, as injected naloxone would rapidly reverse the effects of buprenorphine.

Type

Small Molecule

Groups

Approved, Vet approved

Structure

Similar Structures

Weight: Average: 327.3743
Monoisotopic: 327.147058165
Chemical Formula: C₁₉H₂₁NO₄

Synonyms

(−)-naloxone
1-N-Allyl-14-hydroxynordihydromorphinone
17-allyl-3,14-dihydroxy-4,5α-epoxymorphinan-6-one
Nalossone
Naloxona
Naloxone
Naloxonum

External IDs

EN 1530 Base

Pharmacology

Indication

For the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids including natural and synthetic narcotics, propoxyphene, methadone and the narcotic-antagonist analgesics: nalbuphine, pentazocine and butorphanol. It is also indicated for the diagnosis of suspected acute opioid overdose. It may also be used as an adjunctive agent to increase blood pressure in the management of septic shock.

Associated Conditions

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

Learn More

Pharmacodynamics

Naloxone is an opiate antagonist and prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. In the absence of narcotics or agonistic effects of other narcotic antagonists, it exhibits essentially no pharmacologic activity.

Mechanism of action

While the mechanism of action of naloxone is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the opioid effects by competing for the same receptor sites, especially the mu-opioid receptor. Recently, naloxone has been shown to bind all three opioid receptors (mu, kappa and gamma) but the strongest binding is to the mu receptor.

Target	Actions	Organism
AMu-type opioid receptor	antagonist	Humans
ADelta-type opioid receptor	antagonist	Humans
AKappa-type opioid receptor	antagonist	Humans
NCyclic AMP-responsive element-binding protein 1	other/unknown	Humans
NEstrogen receptor alpha	antagonist other/unknown	Humans
UToll-like receptor 4	inhibitor	Humans
ULiver carboxylesterase 1	Not Available	Humans

Absorption

Tmax: 0.4mg IM injection = 0.38 hr Nasal spray (one 2mg spray) = 0.33 hr Nasal spray (one 4mg spray) = 0.50 hr

Cmax: 0.4mg IM injection = 0.88 ng/mL Nasal spray (one 2mg spray) = 2.91 ng/mL Nasal spray (one 4mg spray) = 4.83 ng/mL

Volume of distribution

Following parenteral administration naloxone hydrochloride is rapidly distributed in the body. Naloxone is also very lipophillic and easily crosses the blood-brain-barrier. It can also cross the placenta.

Protein binding

Plasma protein binding occurs but is relatively weak. Plasma albumin is the major binding constituent but significant binding of naloxone also occurs to plasma constituents other than albumin.

Metabolism

Naloxone is hepatically metabolized and primarily undergoes glucuronidation to form naloxone-3-glucuronide.

Route of elimination

Urine (25%- 40% is excreted as metabolites within 6 hours)

Half-life

0.4mg IM injection = 1.24 hr Nasal spray (one 2mg spray) = 1.85 hr Nasal spray (one 4mg spray) = 2.08 hr

Clearance

Not Available

Adverse Effects

Learn about our commercial Adverse Effects data.

Learn More

Toxicity

LD50, IV administration, mouse = 150 ± 5 mg/kg; LD50, IV administration, rat = 109 ± 4 mg/kg;

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Naloxone Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
Abacavir	Abacavir may decrease the excretion rate of Naloxone which could result in a higher serum level.
Abemaciclib	The metabolism of Abemaciclib can be decreased when combined with Naloxone.
Acalabrutinib	The metabolism of Acalabrutinib can be decreased when combined with Naloxone.
Acarbose	Acarbose may decrease the excretion rate of Naloxone which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Naloxone which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Naloxone which could result in a higher serum level.
Acenocoumarol	The serum concentration of Acenocoumarol can be increased when it is combined with Naloxone.
Acetaminophen	Acetaminophen may decrease the excretion rate of Naloxone which could result in a higher serum level.
Acetazolamide	Naloxone may increase the excretion rate of Acetazolamide which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Naloxone which could result in a higher serum level.

Additional Data Available

Extended Description

Available for Purchase

Extended description of the mechanism of action and particular properties of each drug interaction.

Learn more

Severity

Available for Purchase

A severity rating for each drug interaction, from minor to major.

Learn more

Evidence Level

Available for Purchase

A rating for the strength of the evidence supporting each drug interaction.

Learn more

Action

Available for Purchase

An effect category for each drug interaction. Know how this interaction affects the subject drug.

Learn more

Food Interactions

Take separate from meals. When formulated as a buccal film or sublingual form, avoid eating or drinking until the film has completely dissolved.

Products

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Naloxone hydrochloride	F850569PQR	357-08-4	RGPDIGOSVORSAK-STHHAXOLSA-N
Naloxone hydrochloride dihydrate	5Q187997EE	51481-60-8	TXMZWEASFRBVKY-IOQDSZRYSA-N

Product Images

International/Other Brands

Narcanti / Narcon

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Evzio	Injection, solution	0.4 mg/1	Intramuscular; Subcutaneous	Kaleo, Inc	2014-04-03	2018-05-31
Evzio	Injection, solution	2 mg/0.4mL	Intramuscular; Subcutaneous	Kaleo, Inc	2016-10-19	Not applicable
EVZIO(R) NALOXONE HCl	Injection, solution	2 mg/0.4mL	Intramuscular; Subcutaneous	HF Acquisition Co LLC, DBA HealthFirst	2020-01-11	Not applicable
Injectable Naloxone Hydrochloride	Solution		Intramuscular; Intravenous; Subcutaneous	Omega Laboratories Ltd	2016-08-05	Not applicable
Injectable Naloxone Hydrochloride	Solution		Intramuscular; Intravenous; Subcutaneous	Omega Laboratories Ltd	Not applicable	Not applicable
Naloxone HCl Injection - 0.4mg/ml USP	Liquid		Intramuscular; Intravenous; Subcutaneous	Sandoz Canada Incorporated	1995-12-31	Not applicable
Naloxone HCl Injection - 1mg/ml USP	Liquid		Intramuscular; Intravenous; Subcutaneous	Sandoz Canada Incorporated	1995-12-31	Not applicable
Naloxone Hydrochloride	Injection, solution	0.02 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Hospira	2006-05-11	2006-05-11
Naloxone Hydrochloride	Injection	0.4 mg/1mL	Parenteral	International Medication Systems, Limited	2006-04-13	2006-04-13
Naloxone Hydrochloride	Injection, solution	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Hospira	2006-05-11	2006-05-11

Additional Data Available

Application Number

Available for Purchase

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

Learn more

Product Code

Available for Purchase

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

Learn more

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Naloxone Hci	Injection, solution	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Hf Acquisition Co. Llc, Dba Health First	2018-08-18	Not applicable
Naloxone HCl	Injection	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Renaissance Ssa, Llc	2019-12-28	Not applicable
Naloxone Hydrochloride	Injection	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Hikma Pharmaceuticals USA Inc.	1986-09-24	Not applicable
Naloxone Hydrochloride	Injection, solution	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Medical Purchasing Solutions, Llc	2017-02-28	Not applicable
Naloxone Hydrochloride	Injection, solution	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Cardinal Health	2011-07-08	2019-03-31
Naloxone Hydrochloride	Injection, solution	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	TYA Pharmaceuticals	1986-09-24	Not applicable
Naloxone Hydrochloride	Injection, solution	0.4 mg/1mL	Intramuscular; Intravenous; Subcutaneous	Somerset Therapeutics, Llc	2017-08-08	Not applicable
Naloxone Hydrochloride	Injection	1 mg/1mL	Parenteral	General Injectables & Vaccines, Inc.	2014-05-07	Not applicable
Naloxone Hydrochloride	Injection	1 mg/1mL	Parenteral	Remedy Repack	2015-03-10	2017-03-15
Naloxone Hydrochloride	Injection	1 mg/1mL	Parenteral	Physicians Total Care, Inc.	2011-05-05	Not applicable

Additional Data Available

Application Number

Available for Purchase

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

Learn more

Product Code

Available for Purchase

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

Learn more

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Act Buprenorphine/naloxone	Naloxone (2 mg) + Buprenorphine (8 mg)	Tablet	Sublingual	TEVA Canada Limited	2017-09-28	Not applicable
Act Buprenorphine/naloxone	Naloxone (0.5 mg) + Buprenorphine (2 mg)	Tablet	Sublingual	TEVA Canada Limited	2017-09-28	Not applicable
Bunavail	Naloxone hydrochloride dihydrate (0.3 mg/1) + Buprenorphine hydrochloride (2.1 mg/1)	Film	Buccal	BioDelivery Sciences International, Inc.	2014-09-30	2021-02-28
Bunavail	Naloxone hydrochloride dihydrate (1 mg/1) + Buprenorphine hydrochloride (6.3 mg/1)	Film	Buccal	BioDelivery Sciences International, Inc.	2014-09-30	2021-07-31
Bunavail	Naloxone hydrochloride dihydrate (0.7 mg/1) + Buprenorphine hydrochloride (4.2 mg/1)	Film	Buccal	BioDelivery Sciences International, Inc.	2014-09-30	2021-10-31
Buprenorphine and Naloxone	Naloxone (3 mg/1) + Buprenorphine hydrochloride (12 mg/1)	Film, soluble	Buccal; Sublingual	Dr.Reddys Laboratories Inc	2018-06-14	Not applicable
Buprenorphine and Naloxone	Naloxone hydrochloride dihydrate (3 mg/1) + Buprenorphine hydrochloride (12 mg/1)	Film	Buccal; Sublingual	Mylan Pharmaceuticals Inc.	2019-02-20	Not applicable
Buprenorphine and Naloxone	Naloxone hydrochloride dihydrate (0.5 mg/1) + Buprenorphine hydrochloride (2 mg/1)	Tablet	Sublingual	bryant ranch prepack	2016-09-19	Not applicable
Buprenorphine and Naloxone	Naloxone hydrochloride (3 mg/1) + Buprenorphine hydrochloride (12 mg/1)	Film, soluble	Buccal; Sublingual	Indivior Inc.	2019-02-19	2021-04-30
Buprenorphine and Naloxone	Naloxone hydrochloride dihydrate (2 mg/1) + Buprenorphine hydrochloride (8 mg/1)	Tablet	Sublingual	Gemini Laboratories, LLC	2013-02-22	2019-03-22

Chemical Identifiers

UNII: 36B82AMQ7N
CAS number: 465-65-6
InChI Key: UZHSEJADLWPNLE-GRGSLBFTSA-N
InChI: InChI=1S/C19H21NO4/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/t14-,17+,18+,19-/m1/s1
IUPAC Name: (1S,5R,13R,17S)-10,17-dihydroxy-4-(prop-2-en-1-yl)-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one
SMILES: OC1=CC=C2C[C@H]3N(CC=C)CC[C@@]45[C@@H](OC1=C24)C(=O)CC[C@@]35O

References

Synthesis Reference

Bianca Brogmann, Silke Muhlau, Christof Spitzley, "Pharmaceutical preparation containing oxycodone and naloxone." U.S. Patent US20050245556, issued November 03, 2005.

US20050245556

General References

Link [Link]

External Links

Human Metabolome Database: HMDB0015314
KEGG Drug: D08249
KEGG Compound: C07252
PubChem Compound: 5284596
PubChem Substance: 46508816
ChemSpider: 4447644
BindingDB: 54795
RxNav: 7242
ChEBI: 7459
ChEMBL: CHEMBL80
ZINC: ZINC000000389747
Therapeutic Targets Database: DAP000097
PharmGKB: PA450586
Guide to Pharmacology: GtP Drug Page
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Naloxone

AHFS Codes

28:10.00 — Opiate Antagonists

MSDS

Download (74 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Supportive Care	Back Pain Lower Back	1
4	Completed	Prevention	Opioid Induced Constipation (OIC) / Postoperative pain	1
4	Completed	Prevention	Respiratory Depression	1
4	Completed	Supportive Care	Malignancies	1
4	Completed	Supportive Care	Pain, Chronic	1
4	Completed	Supportive Care	Spinal Disorders	1
4	Completed	Treatment	Back Pain Lower Back	1
4	Completed	Treatment	Back Pain Lower Back / Back Pain, Unspecified / Neuropathic Pain	1
4	Completed	Treatment	Back Pain, Unspecified / Osteoarthritis (OA)	1
4	Completed	Treatment	Chronic Hepatitis C Infection With Hepatic Coma / Hepatic Failure / Hepatic Impairment	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Amphastar Pharmaceuticals
A-S Medication Solutions LLC
Bristol-Myers Squibb Co.
Bryant Ranch Prepack
Cardinal Health
Dispensing Solutions
Diversified Healthcare Services Inc.
Endo Pharmaceuticals Inc.
General Injectables and Vaccines Inc.
Hospira Inc.
Lake Erie Medical and Surgical Supply
Letco Medical Inc.
Mallinckrodt Inc.
Mckesson Corp.
Nucare Pharmaceuticals Inc.
Physicians Total Care Inc.
Reckitt Benckiser Inc.
Southwood Pharmaceuticals
Stat Rx Usa

Dosage Forms

Form	Route	Strength
Tablet, orally disintegrating	Sublingual	1 MG
Tablet, orally disintegrating	Sublingual	2 MG
Film	Buccal
Tablet, orally disintegrating	Sublingual	0.5 mg
Tablet, orally disintegrating	Sublingual	4 mg
Tablet, orally disintegrating	Sublingual	8 mg
Tablet	Oral	2 MG
Tablet	Oral	8 MG
Film	Buccal; Sublingual
Film, soluble	Buccal; Sublingual
Injection, solution		400 mcg/1mL
Injection, solution	Intramuscular; Subcutaneous	0.4 mg/1
Injection, solution	Intramuscular; Subcutaneous	2 mg/0.4mL
Injection, solution	Parenteral	0.4 mg/ml
Injection	Intramuscular; Intravenous	0.4 MG/ML
Injection	Intramuscular; Intravenous; Subcutaneous	0.4 mg/ml
Solution	Parenteral	0.4 mg
Solution	Intramuscular; Intravenous; Subcutaneous	0.4 mg
Spray	Nasal	3.6 MG
Injection, solution		0.4 MG/2ML
Injection, solution		0.4 MG/ML
Injection, solution	Intramuscular; Intravenous; Subcutaneous	0.04 MG/2ML
Injection, solution		0.04 MG/2ML
Injection, solution		0.4 MG/1ML
Liquid	Intramuscular; Intravenous; Subcutaneous
Injection		0.4 mg/2ml
Injection	Intramuscular; Intravenous; Subcutaneous	0.4 mg/1mL
Injection	Intramuscular; Intravenous; Subcutaneous	1 mg/1mL
Injection	Parenteral	0.4 mg/1mL
Injection	Parenteral	1 mg/1mL
Injection	Parenteral	4 mg/1mL
Injection, solution	Intramuscular; Intravenous; Subcutaneous	0.02 mg/1mL
Injection, solution	Intramuscular; Intravenous; Subcutaneous	0.4 mg/1mL
Injection		0.44 mg/2ml
Powder	Not applicable	1 kg/1kg
Solution	Intramuscular; Intravenous; Subcutaneous
Injection		0.4 mg/mL
Injection	Intravenous	0.02 mg/1mL
Injection	Intravenous	0.4 mg/1mL
Injection	Intravenous	1 mg/1mL
Injection, solution		0.04 MG
Injection, solution		0.4 MG
Spray	Nasal	2 mg/0.1mL
Spray	Nasal	4 mg/0.1mL
Spray, metered	Nasal
Injection, solution		40 mg/100mL
Spray	Nasal	1.8 MG
Tablet, extended release	Oral	5 mg
Tablet, extended release	Oral	10 mg
Tablet, extended release	Oral	20 mg
Tablet, extended release	Oral	15 mg
Tablet, extended release	Oral	2.5 mg
Tablet, extended release	Oral	30 mg
Tablet, extended release	Oral	40 mg
Tablet	Oral
Film	Buccal; Sublingual	0.5 MG
Film	Buccal; Sublingual	1 MG
Film	Buccal; Sublingual	2 MG
Film	Buccal; Sublingual	3 MG
Film, soluble	Sublingual
Tablet	Oral; Sublingual	16 MG
Tablet	Oral; Sublingual	2 MG
Tablet	Oral; Sublingual	8 MG
Tablet	Sublingual
Tablet	Sublingual	2 mg
Tablet	Sublingual	0.5 mg
Tablet	Sublingual	8 mg
Film	Sublingual	2 mg
Film	Sublingual	8 mg
Tablet, extended release	Oral
Tablet, film coated, extended release	Oral	5 mg
Tablet, film coated, extended release	Oral	2.5 mg
Tablet, film coated, extended release	Oral
Tablet, extended release	Oral	100 mg
Tablet, extended release	Oral	150 mg
Tablet, extended release	Oral	50 mg
Tablet, extended release	Oral	200 mg
Solution	Oral	50 mg/0.72mL
Solution	Oral	4 mg
Tablet, extended release	Oral	8 mg
Tablet, extended release	Oral	12 mg
Tablet, extended release	Oral	16 mg
Tablet, extended release	Oral	4 mg
Spray	Nasal	1.26 MG
Tablet	Sublingual	0.7 MG
Tablet	Sublingual	1.4 MG
Tablet	Sublingual	11.4 MG
Tablet	Sublingual	2.9 MG
Tablet	Sublingual	5.7 MG
Tablet	Sublingual	8.6 MG
Tablet, orally disintegrating	Sublingual

Prices

Unit description	Cost	Unit
Naloxone hcl powder	70.9USD	g
Naloxone 0.4 mg/ml vial	7.07USD	ml
Naloxone 0.4 mg/ml ampul	4.78USD	ml
Narcan 0.4 mg/ml ampul	4.58USD	ml
Naloxone 0.02 mg/ml vial	0.84USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
US9205082	No	2015-12-08	2022-05-10
US7579019	No	2009-08-25	2020-01-22
US6159498	No	2000-12-12	2016-10-18
US9073933	No	2015-07-07	2025-03-30
US7674800	No	2010-03-09	2025-03-30
US7683072	No	2010-03-23	2025-03-30
US7674799	No	2010-03-09	2025-03-30
US8475832	No	2013-07-02	2030-03-26
US8603514	No	2013-12-10	2024-04-03
US8017150	No	2011-09-13	2023-02-13
US8425462	No	2013-04-23	2024-11-23
US8231573	No	2012-07-31	2028-11-25
US8016788	No	2011-09-13	2025-03-21
US8206360	No	2012-06-26	2027-02-27
US9238108	No	2016-01-19	2027-01-22
US8226610	No	2012-07-24	2029-04-10
US7918823	No	2011-04-05	2024-11-23
US8608698	No	2013-12-17	2024-11-23
US8021344	No	2011-09-20	2029-11-02
US8361029	No	2013-01-29	2024-11-23
US8313466	No	2012-11-20	2024-11-23
US7731690	No	2010-06-08	2025-01-15
US9278182	No	2016-03-08	2026-02-01
US7731686	No	2010-06-08	2026-06-01
US8926594	No	2015-01-06	2026-03-31
US7749194	No	2010-07-06	2028-10-30
US9056170	No	2015-06-16	2024-11-23
US7947017	No	2011-05-24	2028-03-12
US8939943	No	2015-01-27	2031-02-28
US8627816	No	2014-01-14	2032-02-04
US9022022	No	2015-05-05	2031-02-28
US8147866	No	2012-04-03	2027-07-23
US8703177	No	2014-04-22	2032-08-20
US8470361	No	2013-06-25	2030-05-22
US8454996	No	2013-06-04	2019-09-24
US8658198	No	2014-02-25	2027-12-03
US8940330	No	2015-01-27	2032-09-18
US9259421	No	2016-02-16	2032-09-18
US9168252	No	2015-10-27	2022-05-10
US9161937	No	2015-10-20	2022-05-10
US8969369	No	2015-03-03	2022-05-10
US9084729	No	2015-07-21	2022-05-10
US9283216	No	2016-03-15	2022-05-10
US9056051	No	2015-06-16	2022-05-10
US8846090	No	2014-09-30	2023-04-04
US6277384	No	2001-08-21	2018-12-22
US8822487	No	2014-09-02	2018-12-22
US8673355	No	2014-03-18	2018-12-22
US6696066	No	2004-02-24	2018-12-22
US8846091	No	2014-09-30	2023-04-04
US9211253	No	2015-12-15	2035-03-16
US9522919	No	2016-12-20	2025-03-30
US9517307	No	2016-12-13	2034-07-18
US9474869	No	2016-10-25	2031-02-28
US9522188	No	2016-12-20	2035-04-24
US9655843	No	2017-05-23	2027-07-23
US9439900	No	2016-09-13	2032-09-18
US9345701	No	2016-05-24	2022-05-10
US9511066	No	2016-12-06	2022-05-10
US9555000	No	2017-01-31	2023-04-04
US9474750	No	2016-10-25	2018-12-22
US9283221	No	2016-03-15	2022-05-10
US9480644	No	2016-11-01	2035-03-16
US9629965	No	2017-04-25	2035-03-16
US9561177	No	2017-02-07	2035-03-16
US9468747	No	2016-10-18	2035-03-16
US9707226	No	2017-07-18	2035-03-16
US9687454	No	2017-06-27	2029-08-07
US9724471	No	2017-08-08	2027-05-23
US9775838	No	2017-10-03	2035-03-16
US9737669	No	2017-08-22	2024-11-23
US9855221	No	2018-01-02	2022-02-14
US9907793	No	2018-03-06	2023-04-04
US9931305	No	2018-04-03	2022-02-14
US10085937	No	2018-10-02	2035-03-16
US10143972	No	2018-12-04	2031-05-24
US10220158	No	2019-03-05	2035-03-20
US10143792	No	2018-12-04	2031-05-24
US10285910	No	2019-05-14	2022-10-11
US10314977	No	2019-06-11	2024-11-23
US10322239	No	2019-06-18	2031-02-28
US10335549	No	2019-07-02	2025-04-30
US10737028	No	2004-11-23	2024-11-23

Additional Data Available

Filed On

Available for Purchase

The date on which a patent was filed with the relevant government.

Learn more

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	200-205 °C	Not Available
water solubility	Soluble	Not Available
logP	2.09	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	5.64 mg/mL	ALOGPS
logP	1.47	ALOGPS
logP	1.62	ChemAxon
logS	-1.8	ALOGPS
pKa (Strongest Acidic)	10.07	ChemAxon
pKa (Strongest Basic)	7.84	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	5	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	70 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	88.72 m³·mol^-1	ChemAxon
Polarizability	33.83 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9729
Blood Brain Barrier	+	0.9787
Caco-2 permeable	+	0.8867
P-glycoprotein substrate	Substrate	0.8788
P-glycoprotein inhibitor I	Non-inhibitor	0.7922
P-glycoprotein inhibitor II	Non-inhibitor	0.8382
Renal organic cation transporter	Inhibitor	0.5
CYP450 2C9 substrate	Non-substrate	0.8522
CYP450 2D6 substrate	Substrate	0.5296
CYP450 3A4 substrate	Substrate	0.6107
CYP450 1A2 substrate	Non-inhibitor	0.9046
CYP450 2C9 inhibitor	Non-inhibitor	0.9303
CYP450 2D6 inhibitor	Non-inhibitor	0.7886
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.9153
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9523
Ames test	Non AMES toxic	0.7182
Carcinogenicity	Non-carcinogens	0.9583
Biodegradation	Not ready biodegradable	0.9968
Rat acute toxicity	2.7231 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.7798
hERG inhibition (predictor II)	Non-inhibitor	0.8641

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
MS/MS Spectrum - , positive	LC-MS/MS	splash10-004i-0139000000-e70921e0765c3389ce85

Targets

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	2	N/A	N/A	11585443
IC 50 (nM)	23	N/A	N/A	17407276
IC 50 (nM)	7.3	N/A	N/A	14643346 / 17149858 / 17149859
IC 50 (nM)	8.9	N/A	N/A	1320121 / 1335078
Ki (nM)	0.23	N/A	N/A	21482470
Ki (nM)	0.562	N/A	N/A	19527931
Ki (nM)	0.57	N/A	N/A	21621410
Ki (nM)	0.66	N/A	N/A	19027293
Ki (nM)	0.68	N/A	N/A	11495592
Ki (nM)	0.79	N/A	N/A	17407276
Ki (nM)	0.98	N/A	N/A	20055417
Ki (nM)	1.5	N/A	N/A	19836950
Ki (nM)	2.27	N/A	N/A	21621410
Ki (nM)	3.63	N/A	N/A	12747782
Ki (nM)	3.7	N/A	N/A	14643346 / 17149858 / 17149859
Ki (nM)	4.23	N/A	N/A	21621410

Details1. Mu-type opioid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Voltage-gated calcium channel activity
Specific Function: Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name: OPRM1
Uniprot ID: P35372
Uniprot Name: Mu-type opioid receptor
Molecular Weight: 44778.855 Da

References

Narita M, Suzuki M, Mizoguchi H, Narita M, Yajima Y, Sakurada S, Tseng LF, Suzuki T: Up-regulation of mu-opioid receptor-mediated G-protein activation in protein kinase Cgamma knockout mice following repeated naloxone treatment. Neurosci Lett. 2003 Feb 27;338(2):103-6. [PubMed:12566163]
Freye E, Latasch L, Von Bredow G, Neruda B: [The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison]. Schmerz. 1998 Feb 28;12(1):19-24. [PubMed:12799988]
Neal CR Jr, Owens CE, Taylor LP, Hoversten MT, Akil H, Watson SJ Jr: Binding and GTPgammaS autoradiographic analysis of preproorphanin precursor peptide products at the ORL1 and opioid receptors. J Chem Neuroanat. 2003 Jul;25(4):233-47. [PubMed:12842269]
Spetea M, Toth F, Schutz J, Otvos F, Toth G, Benyhe S, Borsodi A, Schmidhammer H: Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist. Eur J Neurosci. 2003 Jul;18(2):290-5. [PubMed:12887410]
Marek GJ: Behavioral evidence for mu-opioid and 5-HT2A receptor interactions. Eur J Pharmacol. 2003 Aug 1;474(1):77-83. [PubMed:12909198]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Helm S, Trescot AM, Colson J, Sehgal N, Silverman S: Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35. [PubMed:18354714]
Goodman AJ, Le Bourdonnec B, Dolle RE: Mu opioid receptor antagonists: recent developments. ChemMedChem. 2007 Nov;2(11):1552-70. [PubMed:17918759]
van Dorp E, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. [PubMed:17367258]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	1000	N/A	N/A	7932177
Ki (nM)	141.3	N/A	N/A	7932177
Ki (nM)	17	N/A	N/A	8114680
Ki (nM)	67.5	N/A	N/A	9686407

Details2. Delta-type opioid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Opioid receptor activity
Specific Function: G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name: OPRD1
Uniprot ID: P41143
Uniprot Name: Delta-type opioid receptor
Molecular Weight: 40368.235 Da

References

Moncada A, Cendan CM, Baeyens JM, Del Pozo E: Effects of serine/threonine protein phosphatase inhibitors on morphine-induced antinociception in the tail flick test in mice. Eur J Pharmacol. 2003 Mar 28;465(1-2):53-60. [PubMed:12650833]
Kakinohana M, Marsala M, Carter C, Davison JK, Yaksh TL: Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia: a clinical and experimental study. Anesthesiology. 2003 Apr;98(4):862-70. [PubMed:12657847]
Breljak D, Boranic M, Horvat S: Oligopeptide fragments of the enkephalin molecule interfere with hematopoietic cell colony formation. Int J Immunopathol Pharmacol. 2000 Jan-Apr;13(1):13-19. [PubMed:12749773]
Chudapongse N, Kim SY, Kramer RE, Ho IK: Nonspecific effects of the selective kappa-opioid receptor agonist U-50,488H on dopamine uptake and release in PC12 cells. J Pharmacol Sci. 2003 Nov;93(3):372-5. [PubMed:14646257]
Osman AM, Gomma M, Saad AH: A possible role for an enkephalinergic system in the internal defense mechanism of Biomphalaria alexandrina exposed to Schistosoma mansoni. J Egypt Soc Parasitol. 2003 Dec;33(3):841-61. [PubMed:14708857]
Helm S, Trescot AM, Colson J, Sehgal N, Silverman S: Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35. [PubMed:18354714]
van Dorp E, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. [PubMed:17367258]

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	10	N/A	N/A	17407276
EC 50 (nM)	6.6	N/A	N/A	12747782
IC 50 (nM)	1.5	N/A	N/A	11585443
IC 50 (nM)	320	N/A	N/A	17407276
IC 50 (nM)	49.8	N/A	N/A	12747782
IC 50 (nM)	50	N/A	N/A	1320121 / 1335078
Ki (nM)	0.25	N/A	N/A	21482470
Ki (nM)	1.1	N/A	N/A	17407276
Ki (nM)	1.2	N/A	N/A	10741545 / 19027293
Ki (nM)	10.7	N/A	N/A	12747782
Ki (nM)	1000	N/A	N/A	7932177
Ki (nM)	13.8	N/A	N/A	7932177
Ki (nM)	14.7	N/A	N/A	20441176
Ki (nM)	2.3	N/A	N/A	8114680
Ki (nM)	2.5	N/A	N/A	9686407
Ki (nM)	3	N/A	N/A	20055417
Ki (nM)	3.2	N/A	N/A	11495592
Ki (nM)	4.47	N/A	N/A	19527931
Ki (nM)	66	N/A	N/A	8057274 / 8410998 / 8410999
Ki (nM)	9.2	N/A	N/A	14643346 / 17149858 / 17149859

Details3. Kappa-type opioid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Opioid receptor activity
Specific Function: G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name: OPRK1
Uniprot ID: P41145
Uniprot Name: Kappa-type opioid receptor
Molecular Weight: 42644.665 Da

References

Peng X, Neumeyer JL: Kappa receptor bivalent ligands. Curr Top Med Chem. 2007;7(4):363-73. [PubMed:17305578]
van Dorp E, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. [PubMed:17367258]
Helm S, Trescot AM, Colson J, Sehgal N, Silverman S: Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35. [PubMed:18354714]

Details4. Cyclic AMP-responsive element-binding protein 1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Other/unknown

General Function: Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function: Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcript...
Gene Name: CREB1
Uniprot ID: P16220
Uniprot Name: Cyclic AMP-responsive element-binding protein 1
Molecular Weight: 36687.86 Da

References

Li J, Li YH, Yuan XR: Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal. Acta Pharmacol Sin. 2003 Sep;24(9):930-6. [PubMed:12956944]
Chartoff EH, Papadopoulou M, Konradi C, Carlezon WA Jr: Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum. J Neurochem. 2003 Oct;87(1):107-18. [PubMed:12969258]
Gao C, Chen LW, Tao YM, Chen J, Xu XJ, Chi ZQ: Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP- response element binding protein in cultured rat hippocampal neurons. Acta Pharmacol Sin. 2003 Dec;24(12):1253-8. [PubMed:14653953]
Walters CL, Cleck JN, Kuo YC, Blendy JA: Mu-opioid receptor and CREB activation are required for nicotine reward. Neuron. 2005 Jun 16;46(6):933-43. [PubMed:15953421]
Hawes JJ, Narasimhaiah R, Picciotto MR: Galanin attenuates cyclic AMP regulatory element-binding protein (CREB) phosphorylation induced by chronic morphine and naloxone challenge in Cath.a cells and primary striatal cultures. J Neurochem. 2006 Feb;96(4):1160-8. Epub 2006 Jan 17. [PubMed:16417577]

Details5. Estrogen receptor alpha

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Antagonist
Other/unknown

General Function: Zinc ion binding
Specific Function: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name: ESR1
Uniprot ID: P03372
Uniprot Name: Estrogen receptor
Molecular Weight: 66215.45 Da

References

Farooqui M, Geng ZH, Stephenson EJ, Zaveri N, Yee D, Gupta K: Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells. Mol Cancer Ther. 2006 Mar;5(3):611-20. [PubMed:16546975]

Details6. Toll-like receptor 4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Transmembrane signaling receptor activity
Specific Function: Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and ...
Gene Name: TLR4
Uniprot ID: O00206
Uniprot Name: Toll-like receptor 4
Molecular Weight: 95679.19 Da

References

Lewis SS, Loram LC, Hutchinson MR, Li CM, Zhang Y, Maier SF, Huang Y, Rice KC, Watkins LR: (+)-naloxone, an opioid-inactive toll-like receptor 4 signaling inhibitor, reverses multiple models of chronic neuropathic pain in rats. J Pain. 2012 May;13(5):498-506. doi: 10.1016/j.jpain.2012.02.005. Epub 2012 Apr 20. [PubMed:22520687]

Details7. Liver carboxylesterase 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Triglyceride lipase activity
Specific Function: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name: CES1
Uniprot ID: P23141
Uniprot Name: Liver carboxylesterase 1
Molecular Weight: 62520.62 Da

References

Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR: Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003 May;10(5):349-56. [PubMed:12679808]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Fang WB, Chang Y, McCance-Katz EF, Moody DE: Determination of naloxone and nornaloxone (noroxymorphone) by high-performance liquid chromatography-electrospray ionization- tandem mass spectrometry. J Anal Toxicol. 2009 Oct;33(8):409-17. doi: 10.1093/jat/33.8.409. [PubMed:19874646]

Details2. UDP-glucuronosyltransferase 1-1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Steroid binding
Specific Function: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name: UGT1A1
Uniprot ID: P22309
Uniprot Name: UDP-glucuronosyltransferase 1-1
Molecular Weight: 59590.91 Da

References

Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Toxic substance binding
Specific Function: Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name: ALB
Uniprot ID: P02768
Uniprot Name: Serum albumin
Molecular Weight: 69365.94 Da

Transporters

Details1. Solute carrier organic anion transporter family member 1A2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Sodium-independent organic anion transmembrane transporter activity
Specific Function: Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name: SLCO1A2
Uniprot ID: P46721
Uniprot Name: Solute carrier organic anion transporter family member 1A2
Molecular Weight: 74144.105 Da

References

Gao B, Hagenbuch B, Kullak-Ublick GA, Benke D, Aguzzi A, Meier PJ: Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier. J Pharmacol Exp Ther. 2000 Jul;294(1):73-9. [PubMed:10871297]

Details2. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524]

Drug created on June 13, 2005 07:24 / Updated on January 19, 2021 22:53

Naloxone

Identification

Structure for Naloxone (DB01183)

Pharmacology

Learn about our commercial Contraindications & Blackbox Warnings data.

Learn about our commercial Adverse Effects data.

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References

References

References

References

References

References

References

Enzymes

References

References

Carriers

Transporters

References

References