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Identification
NameHeroin
Accession NumberDB01452
TypeSmall Molecule
GroupsApproved, Illicit
Description

A 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.

Structure
Thumb
Synonyms
(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
Heroin
morphine diacetate
O,O'-diacetylmorphine
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Heroin hydrochloride
Thumb
  • InChI Key: FZJYQGFGNHGSFX-PVQKIFDLSA-N
  • Monoisotopic Mass: 405.13430059
  • Average Mass: 405.872
DBSALT000095
Categories
UNII70D95007SX
CAS number561-27-3
WeightAverage: 369.411
Monoisotopic: 369.157622851
Chemical FormulaC21H23NO5
InChI KeyInChIKey=GVGLGOZIDCSQPN-PVHGPHFFSA-N
InChI
InChI=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
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
SMILES
[H][C@@]12OC3=C(OC(C)=O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])C=C[C@@H]2OC(C)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Benzylisoquinoline
  • Phenanthrene
  • Tetralin
  • Benzofuran
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Piperidine
  • Acetate salt
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed in the treatment of acute pain, myocardial infarction, acute pulmonary oedema, and chronic pain.
PharmacodynamicsThe onset of heroin's effects is dependent on the method of administration. Taken orally, heroin is totally metabolized in vivo into morphine before crossing the blood-brain barrier; so the effects are the same as oral morphine. Take by injection, heroin crosses into the brain. Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups, therefore, it is known as a prodrug. It is the morphine molecule that then binds with opioid receptors and produces the subjective effects of the heroin high.
Mechanism of actionHeroin 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).
Related Articles
AbsorptionBioavailability is less than 35%.
Volume of distributionNot Available
Protein binding0% (morphine metabolite 35%)
Metabolism

Hepatic.

SubstrateEnzymesProduct
Heroin
6-MonoacetylmorphineDetails
6-Monoacetylmorphine
morphineDetails
Heroin
morphineDetails
Route of elimination90% renal as glucuronides, rest biliary
Half life<10 minutes
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Heroin Action PathwayDrug actionSMP00407
Heroin Metabolism PathwayDrug metabolismSMP00623
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier+0.9892
Caco-2 permeable+0.7924
P-glycoprotein substrateSubstrate0.837
P-glycoprotein inhibitor IInhibitor0.8674
P-glycoprotein inhibitor IINon-inhibitor0.6816
Renal organic cation transporterNon-inhibitor0.5372
CYP450 2C9 substrateNon-substrate0.8192
CYP450 2D6 substrateSubstrate0.6599
CYP450 3A4 substrateSubstrate0.7803
CYP450 1A2 substrateNon-inhibitor0.7994
CYP450 2C9 inhibitorNon-inhibitor0.8162
CYP450 2D6 inhibitorNon-inhibitor0.6335
CYP450 2C19 inhibitorNon-inhibitor0.8059
CYP450 3A4 inhibitorNon-inhibitor0.8072
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8335
Ames testNon AMES toxic0.6935
CarcinogenicityNon-carcinogens0.9341
BiodegradationNot ready biodegradable0.9696
Rat acute toxicity2.8951 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9038
hERG inhibition (predictor II)Non-inhibitor0.9086
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point173 °CPhysProp
boiling point272-274 °C at 1.20E+01 mm HgPhysProp
water solubility600 mg/L (at 25 °C)SEIDELL,A (1941)
logP1.58AVDEEF,A ET AL. (1996)
pKa7.95 (at 25 °C)AVDEEF,A ET AL. (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.266 mg/mLALOGPS
logP2.3ALOGPS
logP1.55ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)9.1ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area65.07 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity98.43 m3·mol-1ChemAxon
Polarizability37.9 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-016u-5955000000-17dd3ef75849a9fb63c3View in MoNA
References
Synthesis ReferenceNot Available
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. [PubMed:12404073 ]
External Links
ATC CodesN07BC06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (18.8 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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 dissociati...
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:16580639 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
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 th...
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. [PubMed: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. [PubMed:18343363 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
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 neurot...
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. [PubMed:18343363 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. Kieffer BL, Gaveriaux-Ruff C: Exploring the opioid system by gene knockout. Prog Neurobiol. 2002 Apr;66(5):285-306. [PubMed:12015197 ]
Comments
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Drug created on July 31, 2007 07:09 / Updated on September 16, 2013 17:14