Naloxone

Synonyms :
1-N-Allyl-14-hydroxynordihydromorphinone, 17-Allyl-3,14-dihydroxy-4,5alpha-epoxymorphinan-6-one, EN 1530 Base, L-Naloxone, N-Allylnoroxymorphone, Nalossone, Naloxona, Naloxone, Naloxonum

Status : approved

Category

Narcotic Antagonists

Therapeutic Classification

ALL OTHER THERAPEUTIC PRODUCTS

VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Central Nervous System Depressants

Description

A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [PubChem]

Used

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.

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 opioid mu 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.

Dosage

Form Route Strength
Tablet sublingual 2; .5 mg/1; mg
Injection, solution intramuscular; subcutaneous .4 mg
Liquid intramuscular; intravenous; subcutaneous 0.4 mg
Liquid intramuscular; intravenous; subcutaneous 1 mg
Injection intramuscular; intravenous; subcutaneous .4 mg/mL
Injection intramuscular; intravenous; subcutaneous 1 mg/mL
Injection parenteral 1 mg/mL
Injection, solution intramuscular; intravenous; subcutaneous .4 mg/mL
Solution intramuscular; intravenous; subcutaneous 1 mg
Solution intramuscular; intravenous; subcutaneous 0.4 mg
Liquid intramuscular; intravenous; subcutaneous 0.02 mg
Tablet oral 50; .5 mg/1; mg
Film, soluble sublingual 12; 3 mg/1; mg
Film, soluble sublingual 2; .5 mg/1; mg
Film, soluble sublingual 4; 1 mg/1; mg
Film, soluble sublingual 8; 2 mg/1; mg
Tablet oral 8; 2 mg/1; mg
Tablet sublingual 2 mg
Tablet sublingual 8 mg
Tablet sublingual 8; 2 mg/1; mg
Tablet (extended-release) oral 10 mg
Tablet (extended-release) oral 2.50 mg
Tablet (extended-release) oral 20 mg
Tablet (extended-release) oral 5 mg
Tablet, orally disintegrating sublingual 1.4; .36 mg/1; mg
Tablet, orally disintegrating sublingual 11.4; 2.9 mg/1; mg
Tablet, orally disintegrating sublingual 5.7; 1.4 mg/1; mg
Tablet, orally disintegrating sublingual 8.6; 2.1 mg/1; mg

Pharmacodynamics

Naloxone is an opiate antagonist and prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine. Naloxone is an essentially pure narcotic antagonist, i.e., it does not possess the “agonistic” or morphine-like properties characteristic of other narcotic antagonists; naloxone does not produce respiratory depression, psychotomimetic effects or pupillary constriction. In the absence of narcotics or agonistic effects of other narcotic antagonists, it exhibits essentially no pharmacologic activity. When given intravenously, the onset of action is apparent within 2 minutes. The onset of action is slower if given subcutaneously or intramuscularly. The duration of action also differs between sites of injection and dose.

Toxic Effect

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

Metabolism

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

Absorption

Well absorbed following intramuscular injection.

Half Life

Adults = 30-81 minutes; Neonates = 3.1 ± 0.5 hours.

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.

Elimination Route

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

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.

Chemical Classification

This compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.

Morphinans

Organic compounds

Alkaloids and derivatives

Morphinans

Salt : Naloxone Hydrochloride

Chemical Name

1-N-Allyl-14-hydroxynordihydromorphinone

Brands

name Dosage form Country
Buprenorphine Hcl and Naloxone Hcl tablet US
Buprenorphine Hcl and Naloxone Hcl tablet US
Evzio injection, solution US
Mylan-buprenorphine/naloxone tablet Canada
Mylan-buprenorphine/naloxone tablet Canada
Naloxone Hcl Injection – 0.4mg/ml USP liquid Canada
Naloxone Hcl Injection – 1mg/ml USP liquid Canada
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection, solution US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride injection US
Naloxone Hydrochloride Injection solution Canada
Naloxone Hydrochloride Injection solution Canada
Naloxone Hydrochloride Injection Sdz Preservative Free solution Canada
Naloxone Hydrochloride Injection USP solution Canada
Narcan Injection 0.02mg/ml liquid Canada
Narcan Injection 0.4mg/ml solution Canada
Narcan Injection 1mg/ml liquid Canada
Pentazocine and Naloxone tablet US
Pentazocine and Naloxone tablet US
Pentazocine and Naloxone tablet US
Pentazocine and Naloxone tablet US
Pentazocine and Naloxone tablet US
Pentazocine and Naloxone tablet US
Pentazocine Hcl and Naloxone Hcl tablet US
Pentazocine Hydrochloride and Naloxone Hydrochloride tablet US
Pentazocine Hydrochloride and Naloxone Hydrochloride tablet US
Suboxone tablet US
Suboxone film, soluble US
Suboxone tablet US
Suboxone film, soluble US
Suboxone film, soluble US
Suboxone film, soluble US
Suboxone film, soluble US
Suboxone film, soluble US
Suboxone tablet Canada
Suboxone tablet Canada
Suboxone tablet US
Suboxone tablet US
Suboxone film, soluble US
Suboxone tablet US
Targin tablet (extended-release) Canada
Targin tablet (extended-release) Canada
Targin tablet (extended-release) Canada
Targin tablet (extended-release) Canada
Teva-buprenorphine/naloxone tablet Canada
Teva-buprenorphine/naloxone tablet Canada
Zubsolv tablet, orally disintegrating US
Zubsolv tablet, orally disintegrating US
Zubsolv tablet, orally disintegrating US
Zubsolv tablet, orally disintegrating US

Drug Drug Interactions

  •  Methylnaltrexone  : May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased.
  •  Naloxegol  : Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased.

Calculated Property

kind Value Source
logP 1.47 ALOGPS
logS -1.8 ALOGPS
Water Solubility 5.64e+00 g/l ALOGPS
logP 1.62 ChemAxon
IUPAC Name (1S,5R,13R,17S)-10,17-dihydroxy-4-(prop-2-en-1-yl)-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10-trien-14-one ChemAxon
Traditional IUPAC Name naloxone ChemAxon
Molecular Weight 327.3743 ChemAxon
Monoisotopic Weight 327.147058165 ChemAxon
SMILES [H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(CC=C)[C@]([H])(C4)[C@]1(O)CCC2=O ChemAxon
Molecular Formula C19H21NO4 ChemAxon
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 ChemAxon
InChIKey InChIKey=UZHSEJADLWPNLE-GRGSLBFTSA-N ChemAxon
Polar Surface Area (PSA) 70 ChemAxon
Refractivity 88.72 ChemAxon
Polarizability 33.8 ChemAxon
Rotatable Bond Count 2 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 2 ChemAxon
pKa (strongest acidic) 7.27 ChemAxon
pKa (strongest basic) 10.63 ChemAxon
Physiological Charge 1 ChemAxon
Number of Rings 5 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Mu-type opioid receptor : in Human
  • Delta-type opioid receptor : in Human
  • Kappa-type opioid receptor : in Human
  • Cyclic AMP-responsive element-binding protein 1 : in Human
  • Estrogen receptor : in Human
  • Toll-like receptor 4 : in Human