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Record Information
Version2.0
Creation Date2014-08-30 21:04:37 UTC
Update Date2014-12-24 20:26:52 UTC
Accession NumberT3D4562
Identification
Common NameHeroin
ClassSmall Molecule
DescriptionA narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed) Internationally, heroin is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs. It is illegal to manufacture, possess, or sell heroin in the United States and the UK. However, under the name diamorphine, heroin is a legal prescription drug in the United Kingdom.
Compound Type
  • Amine
  • Analgesic, Opioid
  • Drug
  • Ester
  • Ether
  • Narcotic
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(5alpha,6alpha)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol diacetate (ester)
3,6-Diacetylmorphine
7,8-Dihydro-4,5-alpha-epoxy-17-methylmorphinan-3,6-alpha-diol diacetate
diacetylmorphine
diamorphine
morphine diacetate
O,O'-diacetylmorphine
Chemical FormulaC21H23NO5
Average Molecular Mass369.411 g/mol
Monoisotopic Mass369.158 g/mol
CAS Registry Number561-27-3
IUPAC Name(1S,5R,13R,14S,17R)-14-(acetyloxy)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-10-yl acetate
Traditional Name(1S,5R,13R,14S,17R)-14-(acetyloxy)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10,15-tetraen-10-yl acetate
SMILES[H][C@@]12OC3=C(OC(C)=O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@]2([H])OC(C)=O
InChI IdentifierInChI=1S/C21H23NO5/c1-11(23)25-16-6-4-13-10-15-14-5-7-17(26-12(2)24)20-21(14,8-9-22(15)3)18(13)19(16)27-20/h4-7,14-15,17,20H,8-10H2,1-3H3/t14-,15+,17-,20-,21-/m0/s1
InChI KeyInChIKey=GVGLGOZIDCSQPN-PVHGPHFFSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Phenanthrene
  • Tetralin
  • Coumaran
  • Alkyl aryl ether
  • Aralkylamine
  • Dicarboxylic acid or derivatives
  • Piperidine
  • Benzenoid
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Tertiary amine
  • Tertiary aliphatic amine
  • Ether
  • Carboxylic acid derivative
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point173 °C
Boiling Point272-274 °C at 1.20E+01 mm Hg
Solubility600 mg/L (at 25 °C)
LogP1.58
Predicted Properties
PropertyValueSource
Water Solubility0.27 g/LALOGPS
logP2.3ALOGPS
logP1.55ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)9.1ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area65.07 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity98.43 m³·mol⁻¹ChemAxon
Polarizability37.9 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-016u-2079000000-b1a98da90b10b2f6fb14JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0009000000-43bbf64aafa84c20e09cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0009000000-d35dead9831fb810a273JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0039000000-3824b8beec641e65acedJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0303-0593000000-b8c7c4e8760df849eeb2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014l-0950000000-9cd1cf455c3a42888ee6JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-024i-0029000000-621a646ce875dfe29a86JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03fr-1049000000-914d38bbfbcc120deba5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-2091000000-4af238bd53e55b1a2237JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00or-2009000000-c77b2701df5a4dd2f03bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05r0-3029000000-ac3b8b35c5f87a9db00bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-9052000000-69d8cee7b68a147f5c7fJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-016u-5955000000-17dd3ef75849a9fb63c3JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureBioavailability is less than 35%.
Mechanism of ToxicityHeroin is a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Heroin, along with other opioids, are agonists to four endogenous neurotransmitters. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present. Endorphins are regularly released in the brain and nerves, attenuating pain. Their other functions are still obscure, but are probably related to the effects produced by heroin besides analgesia (antitussin, anti-diarrheal).
MetabolismHepatic. Route of Elimination: 90% renal as glucuronides, rest biliary Half Life: <10 minutes
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed in the treatment of acute pain, myocardial infarction, acute pulmonary oedema, and chronic pain.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01452
HMDB IDNot Available
PubChem Compound ID5462328
ChEMBL IDCHEMBL459324
ChemSpider ID4575379
KEGG IDC06534
UniProt IDNot Available
OMIM ID
ChEBI ID27808
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkHeroin
References
Synthesis ReferenceNot Available
MSDST3D4562.pdf
General References
  1. Tschacher W, Haemmig R, Jacobshagen N: Time series modeling of heroin and morphine drug action. Psychopharmacology (Berl). 2003 Jan;165(2):188-93. Epub 2002 Oct 29. [12404073 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
References
  1. Greenwald MK, Johanson CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA, Schuster CR, Zubieta JK: Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology. 2003 Nov;28(11):2000-9. [12902992 ]
  2. Becker J, Schmidt P, Musshoff F, Fitzenreiter M, Madea B: MOR1 receptor mRNA expression in human brains of drug-related fatalities-a real-time PCR quantification. Forensic Sci Int. 2004 Feb 10;140(1):13-20. [15013161 ]
  3. Yao L, McFarland K, Fan P, Jiang Z, Inoue Y, Diamond I: Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8746-51. Epub 2005 Jun 3. [15937104 ]
  4. Antonilli L, Petecchia E, Caprioli D, Badiani A, Nencini P: Effect of repeated administrations of heroin, naltrexone, methadone, and alcohol on morphine glucuronidation in the rat. Psychopharmacology (Berl). 2005 Oct;182(1):58-64. Epub 2005 Sep 29. [15986196 ]
  5. Choi HS, Kim CS, Hwang CK, Song KY, Wang W, Qiu Y, Law PY, Wei LN, Loh HH: The opioid ligand binding of human mu-opioid receptor is modulated by novel splice variants of the receptor. Biochem Biophys Res Commun. 2006 May 19;343(4):1132-40. Epub 2006 Mar 23. [16580639 ]
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 nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Klein G, Juni A, Arout CA, Waxman AR, Inturrisi CE, Kest B: Acute and chronic heroin dependence in mice: contribution of opioid and excitatory amino acid receptors. Eur J Pharmacol. 2008 May 31;586(1-3):179-88. doi: 10.1016/j.ejphar.2008.02.035. Epub 2008 Feb 19. [18343363 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  3. Kieffer BL, Gaveriaux-Ruff C: Exploring the opioid system by gene knockout. Prog Neurobiol. 2002 Apr;66(5):285-306. [12015197 ]
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 synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
References
  1. Wee S, Koob GF: The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. Psychopharmacology (Berl). 2010 Jun;210(2):121-35. doi: 10.1007/s00213-010-1825-8. Epub 2010 Mar 30. [20352414 ]
  2. Klein G, Juni A, Arout CA, Waxman AR, Inturrisi CE, Kest B: Acute and chronic heroin dependence in mice: contribution of opioid and excitatory amino acid receptors. Eur J Pharmacol. 2008 May 31;586(1-3):179-88. doi: 10.1016/j.ejphar.2008.02.035. Epub 2008 Feb 19. [18343363 ]
General Function:
Zinc ion binding
Specific Function:
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name:
MT2A
Uniprot ID:
P02795
Molecular Weight:
6042.05 Da
References
  1. Brzezinski MR, Spink BJ, Dean RA, Berkman CE, Cashman JR, Bosron WF: Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs. Drug Metab Dispos. 1997 Sep;25(9):1089-96. [9311626 ]