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Identification
Name Naloxone
Accession Number DB01183 (APRD00025)
Type small molecule
Groups approved
Description

A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • EN 1530 Base
  • L-Naloxone
  • N-Allylnoroxymorphone
  • Nalossone [Dcit]
  • Naloxona [INN-Spanish]
  • Naloxone HCl
  • Naloxonum [INN-Latin]
Brand names
  • Nalone
  • Narcan
  • Narcanti
  • Narcon
Brand name mixtures Not Available
Categories
  • Antinarcotic Agents
  • Narcotic Antagonists
  • Depressants
  • Opiate Antagonists
CAS number 465-65-6
Weight Average: 327.3743
Monoisotopic: 327.147058165
Chemical Formula C19H21NO4
InChI Key InChIKey=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
Plain Text
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
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(CC=C)[C@]([H])(C4)[C@]1(O)CCC2=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Morphinans
  • Benzylisoquinolines
Substructures
  • Morphinans
  • Benzofurans
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Naphthalenes
  • Phenols and Derivatives
  • Benzylisoquinolines
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Methoxyphenols
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Phenanthrenes
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Cyclohexenes and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
  • Piperidines
  • Ketones
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.
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.
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.
Absorption Well absorbed following intramuscular injection.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life 30-81 minutes
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Wyeth ayerst laboratories
  • Abraxis pharmaceutical products
  • Astrazeneca lp
  • Hospira inc
  • International medication systems ltd
  • International medication system
  • Marsam pharmaceuticals llc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Watson laboratories inc
  • Bristol myers squibb pharma co
  • Endo pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices
Unit description Cost Unit
Naloxone hcl powder 70.9 USD g
Naloxone 0.4 mg/ml vial 7.07 USD ml
Naloxone 0.4 mg/ml ampul 4.78 USD ml
Narcan 0.4 mg/ml ampul 4.58 USD ml
Naloxone 0.02 mg/ml vial 0.84 USD ml
Patents Not Available
Properties
State solid
Melting point 200 - 205 oC
Experimental Properties
Property Value Source
water solubility Soluble PhysProp
logP 0.6 PhysProp
Predicted Properties
Property Value Source
water solubility 5.64e+00 g/l ALOGPS
logP 1.47 ALOGPS
logP 1.62 ChemAxon Molconvert
logS -1.76 ALOGPS
pKa 13.58 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 70.00 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 88.72 ChemAxon Molconvert
polarizability 33.80 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07252 Link_out
PubChem Compound 5284596 Link_out
PubChem Substance 46508816 Link_out
ChemSpider 4447644 Link_out
ChEBI 7459 Link_out
ChEMBL 7459 Link_out
Therapeutic Targets Database DAP000097 Link_out
PharmGKB PA450586 Link_out
Drug Product Database 2148706 Link_out
RxList http://www.rxlist.com/cgi/generic3/naloxone.htm Link_out
Drugs.com http://www.drugs.com/cdi/naloxone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Naloxone Link_out
ATC Codes
  • V03AB15
AHFS Codes
  • 28:10.00
PDB Entries Not Available
FDA label Not Available
MSDS show (74 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. Marek GJ: Behavioral evidence for mu-opioid and 5-HT2A receptor interactions. Eur J Pharmacol. 2003 Aug 1;474(1):77-83. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. 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
  8. Goodman AJ, Le Bourdonnec B, Dolle RE: Mu opioid receptor antagonists: recent developments. ChemMedChem. 2007 Nov;2(11):1552-70. Pubmed
  9. van Dorp EL, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. Pubmed

2. Delta-type opioid receptor

Pharmacological action: yes
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. Breljak D, Boranic M, Horvat S: Oligopeptide fragments of the enkephalin molecule interfere with hematopoietic cell colony formation. Int J Immunopathol Pharmacol. 2000 Jan;13(1):13-19. Pubmed
  4. 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
  5. 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
  6. 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
  7. van Dorp EL, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. Pubmed

3. Kappa-type opioid receptor

Pharmacological action: yes
Actions: antagonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions

Organism class: human
UniProt ID: P41145 Link_out
Gene: OPRK1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Peng X, Neumeyer JL: Kappa receptor bivalent ligands. Curr Top Med Chem. 2007;7(4):363-73. Pubmed
  2. van Dorp EL, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. Pubmed
  3. 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

4. cAMP response element-binding protein

Pharmacological action: no
Actions: other/unknown

This protein binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. CREB stimulates transcription on binding to the CRE

Organism class: human
UniProt ID: P16220 Link_out
Gene: CREB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

5. Estrogen receptor

Pharmacological action: no
Actions: other/unknown

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 tissues

Organism class: human
UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Enzymes

1. Cytochrome P450 2C8

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A4

Actions: substrate

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

2. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:09

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.