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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H16O6.2C19H21NO4
Molecular Weight 1043.1182
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DINALOXONE PAMOATE

SMILES

OC1=CC=C2C[C@H]3N(CC=C)CC[C@@]45[C@@H](OC1=C24)C(=O)CC[C@@]35O.OC6=CC=C7C[C@H]8N(CC=C)CC[C@@]9%10[C@@H](OC6=C79)C(=O)CC[C@@]8%10O.OC(=O)C%11=CC%12=CC=CC=C%12C(CC%13=C(O)C(=CC%14=CC=CC=C%13%14)C(O)=O)=C%11O

InChI

InChIKey=BFXHRYXMFBRRFN-SXYFAJAHSA-N
InChI=1S/C23H16O6.2C19H21NO4/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;2*1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11/h1-10,24-25H,11H2,(H,26,27)(H,28,29);2*2-4,14,17,21,23H,1,5-10H2/t;2*14-,17+,18+,19-/m.11/s1

HIDE SMILES / InChI

Molecular Formula C23H16O6
Molecular Weight 388.3695
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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

4.0348799E10
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

4.0348799E10
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

4.0348799E10
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
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
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
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
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
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
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)
n = 12
Health Status: healthy
Age Group: 23.8 years (range: 22.6–25 years)
Sex: M+F
Population Size: 12
Sources:
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
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
n = 28
Health Status: healthy
Age Group: adult
Population Size: 28
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypertension 1 patient
Disc. AE
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Myoclonus 1 patient
Disc. AE
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Bradycardia 2 patients
Disc. AE
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Hypotension 3 patients
Disc. AE
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Agitation 3%
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Nausea 32%
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Confusion 5%
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Emesis 5%
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Headache 5%
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
Seizures 5%
160 mg/m2 single, intravenous (starting)
Highest studied dose
Dose: 160 mg/m2
Route: intravenous
Route: single
Dose: 160 mg/m2
Sources:
unhealthy, 35-85 years
n = 38
Health Status: unhealthy
Condition: acute ischemic stroke
Age Group: 35-85 years
Population Size: 38
Sources:
PubMed

PubMed

TitleDatePubMed
Naloxone-induced bradycardia in pithed rats: evidence for an interaction with the peripheral sympathetic nervous system and alpha-2 adrenoceptors.
1992 Dec
Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain.
1992 Jan
Chronic naloxone administration, a potential treatment for migraine, enhances morphine-induced miosis.
1992 Jul
Methadone, ciprofloxacin, and adverse drug reactions.
2000 Dec 16
Orphanin FQ/nociceptin inhibits morphine withdrawal.
2000 Jan 14
Differential cardiorespiratory effects of endomorphin 1, endomorphin 2, DAMGO, and morphine.
2000 Sep
Relief by naloxone of morphine-induced spasm of the sphincter of Oddi in a post-cholecystectomy patient.
2001 Aug
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
Ethological analysis of morphine withdrawal with different dependence programs in male mice.
2002 Feb
The role of spinal neuropeptides and prostaglandins in opioid physical dependence.
2002 May
Naloxone increases pain induced by topical capsaicin in healthy human volunteers.
2002 Sep
Attitudes about prescribing take-home naloxone to injection drug users for the management of heroin overdose: a survey of street-recruited injectors in the San Francisco Bay Area.
2003 Jun
Preliminary evidence of health care provider support for naloxone prescription as overdose fatality prevention strategy in New York City.
2003 Jun
Human carboxylesterase 1: from drug metabolism to drug discovery.
2003 Jun
Safety of enteral naloxone and i.v. neostigmine when used to relieve constipation.
2003 Jun 15
Heroin addicts to receive CPR training and Narcan.
2003 May
Naloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humans.
2003 Nov
Pharmacokinetics of high-dose buprenorphine following single administration of sublingual tablet formulations in opioid naïve healthy male volunteers under a naltrexone block.
2003 Oct 24
Systemic morphine-induced release of serotonin in the rostroventral medulla is not mimicked by morphine microinjection into the periaqueductal gray.
2003 Sep
Bovine lactoferrin has a nitric oxide-dependent hypotensive effect in rats.
2004 Feb
Narcan use in the endoscopy lab: an important component of patient safety.
2004 Jan-Feb
Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.
2004 Jun 1
[Effect of nitric oxide synthase inhibitor on the testis cell apoptosis in morphine-dependent rats].
2004 Nov
Effects of L-745,870, a dopamine D4 receptor antagonist, on naloxone-induced morphine dependence in mice.
2004 Oct
Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats.
2004 Oct
Rapid, transient, and dose-dependent expression of hsp70 messenger RNA in the rat brain after morphine treatment.
2004 Summer
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Effective opiate-receptor antagonist therapy of cholestatic pruritus induced by an oral contraceptive.
2005 May
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 Thu Jul 06 20:03:20 UTC 2023
Edited
by admin
on Thu Jul 06 20:03:20 UTC 2023
Record UNII
P7WJA2YB2Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DINALOXONE PAMOATE
Common Name English
2-NAPHTHALENECARBOXYLIC ACID, 4,4'-METHYLENEBIS(3-HYDROXY-, COMPD. WITH (5.ALPHA.)-4,5-EPOXY-3,14-DIHYDROXY-17-(2-PROPENYL)MORPHINAN-6-ONE (1:2)
Systematic Name English
MORPHINAN-6-ONE, 4,5-EPOXY-3,14-DIHYDROXY-17-(2-PROPENYL)-, (5.ALPHA.)-, 4,4'-METHYLENEBIS(3-HYDROXY-2-NAPHTHALENECARBOXYLATE) (2:1) (SALT)
Systematic Name English
Code System Code Type Description
CAS
36415-94-8
Created by admin on Thu Jul 06 20:03:20 UTC 2023 , Edited by admin on Thu Jul 06 20:03:20 UTC 2023
PRIMARY
PUBCHEM
133082440
Created by admin on Thu Jul 06 20:03:21 UTC 2023 , Edited by admin on Thu Jul 06 20:03:21 UTC 2023
PRIMARY
CAS
83213-70-1
Created by admin on Thu Jul 06 20:03:21 UTC 2023 , Edited by admin on Thu Jul 06 20:03:21 UTC 2023
NON-SPECIFIC STOICHIOMETRY
FDA UNII
P7WJA2YB2Y
Created by admin on Thu Jul 06 20:03:21 UTC 2023 , Edited by admin on Thu Jul 06 20:03:21 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY