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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H21NO4.ClH
Molecular Weight 363.835
Optical Activity ( - )
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NALOXONE HYDROCHLORIDE

SMILES

Cl.OC1=C2O[C@H]3C(=O)CC[C@@]4(O)[C@H]5CC(C=C1)=C2[C@@]34CCN5CC=C

InChI

InChIKey=RGPDIGOSVORSAK-STHHAXOLSA-N
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

HIDE SMILES / InChI

Molecular Formula C19H21NO4
Molecular Weight 327.3743
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Naloxone, sold under the brand name Narcan among others, is a medication used to block the effects of opioids, especially in overdose. Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system (CNS). Naloxone is a μ-opioid receptor (MOR) inverse agonist, and 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). If administered in the absence of concomitant opioid use, no functional pharmacological activity occurs (except the inability for the body to combat pain naturally). In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. 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. When administered parenterally (e.g. intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine. Naloxone is useful both in acute opioid overdose and in reducing respiratory or mental depression due to opioids. Whether it is useful in those in cardiac arrest due to an opioid overdose is unclear. Naloxone is poorly absorbed when taken by mouth, so it is commonly combined with a number of oral opioid preparations, including buprenorphine and pentazocine, so that when taken orally, just the opioid has an effect, but if misused by injecting, the naloxone blocks the effect of the opioid. In a meta-analysis of people with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, those who received naloxone had improved blood flow. Naloxone is also experimentally used in the treatment for congenital insensitivity to pain with anhidrosis, an extremely rare disorder (one in 125 million) that renders one unable to feel pain or differentiate temperatures. Naloxone can also be used as an antidote in overdose of clonidine, a medication that lowers blood pressure.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.3 nM [IC50]
49.8 nM [IC50]
138.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NARCAN

Approved Use

Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for the relief of moderate to severe pain. Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for oral use only.

Launch Date

1971
Primary
NARCAN

Approved Use

Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for the relief of moderate to severe pain. Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for oral use only.

Launch Date

1971
Primary
NARCAN

Approved Use

Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for the relief of moderate to severe pain. Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for oral use only.

Launch Date

1971
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.09 ng/mL
10 mg/kg single, nasal
dose: 10 mg/kg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4.83 ng/mL
4 mg single, nasal
dose: 4 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
0.87 ng/mL
0.4 mg single, intramuscular
dose: 0.4 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9.62 ng/mL
8 mg single, nasal
dose: 8 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
37.1 ng × min/mL
10 mg/kg single, nasal
dose: 10 mg/kg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
7.9 ng × h/mL
4 mg single, nasal
dose: 4 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.68 ng × h/mL
0.4 mg single, intramuscular
dose: 0.4 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
15 ng × h/mL
8 mg single, nasal
dose: 8 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
28.2 min
10 mg/kg single, nasal
dose: 10 mg/kg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
1.2 h
0.4 mg single, intramuscular
dose: 0.4 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
2.1 h
8 mg single, nasal
dose: 8 mg
route of administration: Nasal
experiment type: SINGLE
co-administered:
NALOXONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
0.8 mg single, intramuscular
Dose: 0.8 mg
Route: intramuscular
Route: single
Dose: 0.8 mg
Sources:
healthy, 23.8 years (range: 22.6–25 years)
Health Status: healthy
Age Group: 23.8 years (range: 22.6–25 years)
Sex: M+F
Sources:
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Disc. AE: Hypotension, Bradycardia...
Other AEs: Nausea, Emesis...
AEs leading to
discontinuation/dose reduction:
Hypotension (3 patients)
Bradycardia (2 patients)
Myoclonus (1 patient)
Hypertension (1 patient)
Other AEs:
Nausea (32%)
Emesis (5%)
Seizures (5%)
Headache (5%)
Confusion (5%)
Agitation (3%)
Sources:
8 mg single, intranasal
Dose: 8 mg
Route: intranasal
Route: single
Dose: 8 mg
Sources:
healthy, adult
AEs

AEs

AESignificanceDosePopulation
Hypertension 1 patient
Disc. AE
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Myoclonus 1 patient
Disc. AE
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Bradycardia 2 patients
Disc. AE
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Hypotension 3 patients
Disc. AE
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Agitation 3%
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Nausea 32%
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Confusion 5%
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Emesis 5%
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Headache 5%
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
Seizures 5%
160 mg/m2 single, intravenous
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
Health Status: unhealthy
Age Group: 35-85 years
Sources:
PubMed

PubMed

TitleDatePubMed
Changes in benzodiazepine-receptor activity modify morphine withdrawal syndrome in mice.
1992 Aug
The NMDA receptor antagonist MK-801 prevents long-lasting non-associative morphine tolerance in the rat.
1992 Mar 20
Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction.
1998 Dec
Neurotransmitter-mediated open-field behavioral action of CGRP.
1999
Repressive/defensive coping, endogenous opioids and health: how a life so perfect can make you sick.
1999 Jan 18
[The discriminative stimulus properties of naloxone during dissociative learning in a Y maze in morphine-dependent rats].
1999 Jan-Feb
Modification of naloxone-induced withdrawal signs by dextromethorphan in morphine-dependent mice.
1999 Jul 14
Methadone, ciprofloxacin, and adverse drug reactions.
2000 Dec 16
Fentanyl-induced chest wall rigidity and laryngospasm in preterm and term infants.
2000 Mar
Effect of whole-body vibration in the vertical axis on cortisol and adrenocorticotropic hormone levels in piglets.
2001 Apr
Opioid-induced hyperalgesia and incisional pain.
2001 Jul
Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence.
2001 Jun
Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits.
2001 Jun 15
Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect.
2001 May
Delayed opioid withdrawal-like reaction in primary biliary cirrhosis following naloxone therapy.
2001 Sep
Effects of Ferula gummosa Boiss. fractions on morphine dependence in mice.
2001 Sep
Naloxone methiodide reverses opioid-induced respiratory depression and analgesia without withdrawal.
2002 Jun 7
Identification of opioid-regulated genes in human lymphocytic cells by differential display: upregulation of Krüppel-like factor 7 by morphine.
2003 Dec 10
Safety of enteral naloxone and i.v. neostigmine when used to relieve constipation.
2003 Jun 15
Bovine lactoferrin has a nitric oxide-dependent hypotensive effect in rats.
2004 Feb
Magnesium influence on morphine--induced pharmacodependence in rats.
2004 Mar
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.
2004 Nov
[Preclinical management of accidental methadone intoxication of a 4-year-old girl. Antagonist or intubation?].
2004 Oct
Ventricular tachycardia following naloxone administration in an illicit drug misuse.
2005 Aug
Calcitonin gene-related peptide-induced suppression of luteinizing hormone pulses in the rat: the role of endogenous opioid peptides.
2005 Aug 1
Effect of fentanyl on lidocaine-induced convulsions in mice.
2005 Dec
[Effect of naloxone on expression of Bcl-2 protein and tumor necrosis factor-alpha in rats with acute myocardial ischemia/reperfusion injury].
2005 Jul
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells.
2005 Nov
Patents

Sample Use Guides

Opioid Overdose–Known or Suspected: An initial dose of 0.4 mg to 2 mg of NARCAN may be administered intravenously. If the desired degree of counteraction and improvement in respiratory functions are not obtained, it may be repeated at two- to three-minute intervals. If no response is observed after 10 mg of NARCAN have been administered, the diagnosis of opioid-induced or partial opioid-induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if the intravenous route is not available. Postoperative Opioid Depression: For the partial reversal of opioid depression following the use of opioids during surgery, smaller doses of NARCAN are usually sufficient. The dose of NARCAN should be titrated according to the patient’s response. For the initial reversal of respiratory depression, NARCAN should be injected in increments of 0.1 to 0.2 mg intravenously at two- to three-minute intervals to the desired degree of reversal, i.e., adequate ventilation and alertness without significant pain or discomfort. Larger than necessary dosage of NARCAN may result in significant reversal of analgesia and increase in blood pressure. Similarly, too rapid reversal may induce nausea, vomiting, sweating or circulatory stress. Repeat doses of NARCAN may be required within one- to two-hour intervals depending upon the amount, type (i.e., short or long acting) and time interval since last administration of an opioid. Supplemental intramuscular doses have been shown to produce a longer lasting effect.
Route of Administration: Other
MDCKII-MDR1 assay. Stock solutions of Naloxone (20 mM) were prepared in 100% DMSO and then diluted to the final concentration of 10 mkM, in Dulbecco’s PBS. Naloxone were tested in both directions, apicalto-basolateral (A→B) and basolateral-to-apical (B→A), in duplicate. The ratio BA/AB >2 indicates an efflux phenomena. Permeability studies were conducted at 37 ◦C in incubator for 60 min. The monolayer integrity was evaluated by measuring the TransEpithelial Electrical Resistance (TEER) by using the Millicell-ERS system (Millipore Corporation) and it was considered integer if the resistancewas between 200 and 300 cm2. After the transport study the monolayer integrity was measured in each well by adding a 0.02 mg/mL solution of lucifer yellow (LY); the test was conducted at 37 ◦C for 60 min, and the fluorescence (RFU) was measured at 485/535 nm.
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:48:16 GMT 2025
Edited
by admin
on Mon Mar 31 17:48:16 GMT 2025
Record UNII
F850569PQR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NALOXONE HYDROCHLORIDE
GREEN BOOK   MART.   MI   ORANGE BOOK   USAN   USP   VANDF   WHO-DD  
USAN  
Official Name English
SUBOXONE COMPONENT NALOXONE HYDROCHLORIDE
Preferred Name English
ANHYDROUS NALOXONE HYDROCHLORIDE
Common Name English
NALOXONE HYDROCHLORIDE [JAN]
Common Name English
NARCANTI
Common Name English
EN-15304
Code English
REZENOPY
Brand Name English
NALOXONE HYDROCHLORIDE [MART.]
Common Name English
NALOXONE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
NALOXONE HYDROCHLORIDE [MI]
Common Name English
(-)-N-ALLYL-14-HYDROXYNORDIHYDROMORPHINONE HYDROCHLORIDE
Common Name English
RIVIVE
Brand Name English
NALOXONE HCL
Common Name English
NALOXONE HYDROCHLORIDE [GREEN BOOK]
Common Name English
TARGINIQ COMPONENT NALOXONE HYDROCHLORIDE
Brand Name English
NALOXONE HYDROCHLORIDE [VANDF]
Common Name English
MORPHINAN-6-ONE, 4,5-EPOXY-3,14-DIHYDROXY-17-(2-PROPENYL)-, HYDROCHLORIDE, (5.ALPHA.)-
Systematic Name English
TALWIN NX COMPONENT NALOXONE HYDROCHLORIDE
Common Name English
Naloxone hydrochloride [WHO-DD]
Common Name English
NSC-757109
Code English
NARCAN
Brand Name English
NALOXONE HYDROCHLORIDE [USAN]
Common Name English
NALOXONE HYDROCHLORIDE ANHYDROUS [WHO-IP]
Common Name English
EVZIO
Brand Name English
17-Allyl-4,5?-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride
Systematic Name English
NALOXONE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
NALOXONI HYDROCHLORIDUM ANHYDROUS [WHO-IP LATIN]
Common Name English
NIH 7890
Code English
KLOXXADO
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C681
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
Code System Code Type Description
SMS_ID
100000091649
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
NCI_THESAURUS
C678
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
RXCUI
203192
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY RxNorm
EVMPD
SUB03382MIG
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
CAS
357-08-4
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
EPA CompTox
DTXSID70957097
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
FDA UNII
F850569PQR
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
NSC
757109
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
DRUG BANK
DBSALT000126
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
ECHA (EC/EINECS)
206-611-0
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
MERCK INDEX
m7717
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY Merck Index
ChEMBL
CHEMBL80
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
PUBCHEM
5464092
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
CHEBI
31892
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
NALOXONE HYDROCHLORIDE
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY Description: A white or almost white powder. Solubility: Soluble in water; slightly soluble in ethanol (~750 g/l) TS; practically insoluble in ether R.Category: Narcotic antagonist. Storage: Naloxone hydrochloride should be kept in a tightly closed container, protected from light. Labelling: The designation on the container of Naloxone hydrochloride should state whether the substance is in the anhydrousform or is the dihydrate. Additional information: Even in the absence of light, Naloxone hydrochloride is gradually degraded on exposure to a humidatmosphere, the decomposition being faster at higher temperatures. It melts at about 177?C. Definition: Naloxone hydrochloride contains not less than 98.0% and not more than 102.0% of C19H21NO4,HCl, calculated withreference to the dried substance.
EVMPD
SUB25206
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
DAILYMED
F850569PQR
Created by admin on Mon Mar 31 17:48:16 GMT 2025 , Edited by admin on Mon Mar 31 17:48:16 GMT 2025
PRIMARY
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ACTIVE MOIETY