Identification

Name
Heroin
Accession Number
DB01452
Type
Small Molecule
Groups
Illicit, Investigational
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
  • (5α,6α)-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
  • O,O'-Diacetylmorphine
External IDs
IDS-NH-001 / IDS-NH-001(SECT.3) / J6.494G
Product Ingredients
IngredientUNIICASInChI Key
Heroin hydrochloride8H672SHT8E1502-95-0FZJYQGFGNHGSFX-PVQKIFDLSA-N
Categories
UNII
70D95007SX
CAS number
561-27-3
Weight
Average: 369.411
Monoisotopic: 369.157622851
Chemical Formula
C21H23NO5
InChI Key
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

Pharmacology

Indication

Used in the treatment of acute pain, myocardial infarction, acute pulmonary oedema, and chronic pain.

Pharmacodynamics

The 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 action

Heroin 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).

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
UKappa-type opioid receptor
agonist
Human
UDelta-type opioid receptor
agonist
Human
ULiver carboxylesterase 1Not AvailableHuman
Absorption

Bioavailability is less than 35%.

Volume of distribution
Not Available
Protein binding

0% (morphine metabolite 35%)

Metabolism

Hepatic.

Route of elimination

90% renal as glucuronides, rest biliary

Half life

<10 minutes

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Heroin Metabolism PathwayDrug metabolism
Heroin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may increase the analgesic activities of Heroin.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Heroin.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Heroin.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Heroin.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Heroin is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Heroin is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of adverse effects can be increased when Heroin is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Heroin is combined with Aceprometazine.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Heroin.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Heroin.
Food Interactions
  • Avoid alcohol
  • To avoid constipation: increase your daily intake of fiber (beans, whole grains, vegetables).

References

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
KEGG Drug
D07286
KEGG Compound
C06534
PubChem Compound
5462328
PubChem Substance
46506839
ChemSpider
4575379
ChEBI
27808
ChEMBL
CHEMBL459324
PharmGKB
PA452619
Drugs.com
Drugs.com Drug Page
Wikipedia
Heroin
ATC Codes
N07BC06 — Diamorphine
MSDS
Download (18.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentOpioids1
3CompletedBasic ScienceHeroin Dependence1
3CompletedBasic ScienceOpioid-Related Disorders1
3CompletedTreatmentHeroin Dependence / Opioid Dependence1
3CompletedTreatmentOpioid Dependence1
Not AvailableCompletedSupportive CareCancers1
Not AvailableCompletedTreatmentColorectal Cancers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)173 °CPhysProp
boiling point (°C)272-274 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-016u-5955000000-17dd3ef75849a9fb63c3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0009000000-43bbf64aafa84c20e09c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0009000000-d35dead9831fb810a273
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0039000000-3824b8beec641e65aced
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0303-0593000000-b8c7c4e8760df849eeb2
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-014l-0950000000-9cd1cf455c3a42888ee6

Taxonomy

Description
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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Morphinans
Sub Class
Not Available
Direct Parent
Morphinans
Alternative Parents
Phenanthrenes and derivatives / Tetralins / Coumarans / Alkyl aryl ethers / Aralkylamines / Piperidines / Dicarboxylic acids and derivatives / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters
show 6 more
Substituents
Morphinan / Phenanthrene / Tetralin / Coumaran / Alkyl aryl ether / Aralkylamine / Dicarboxylic acid or derivatives / Piperidine / Benzenoid / Amino acid or derivatives
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid (CHEBI:27808)

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...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
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 synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
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 n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
substrate for metabolism
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 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. [PubMed:9311626]

Drug created on July 31, 2007 07:09 / Updated on October 01, 2018 16:21