Diamorphine is an opioid analgesic agent used in the relief of severe pain associated with surgical procedures, myocardial infarction or pain in the terminally ill and for the relief of dyspnea in acute pulmonary edema.

Generic Name
DrugBank Accession Number

Diamorphine (heroin) is 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, diamorphine is controlled under Schedules I and IV of the Single Convention on Narcotic Drugs. As heroin, it is illegal to manufacture, possess, or sell in the United States and the UK. However, under the name diamorphine, heroin is a legal prescription drug in the United Kingdom.

Small Molecule
Approved, Illicit, Investigational
Average: 369.411
Monoisotopic: 369.157622851
Chemical Formula
  • (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
  • Heroin
  • O,O'-Diacetylmorphine
External IDs
  • IDS-NH-001
  • IDS-NH-001(SECT.3)
  • J6.494G



Diamorphine, as a prescription medication in the United Kingdom, is indicated for use in the treatment of severe pain associated with surgical procedures, myocardial infarction or pain in the terminally ill and for the relief of dyspnoea in acute pulmonary edema 6.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more

The onset of heroin's effects is dependent on the method of administration. Taken orally, heroin is totally metabolized in vivo via extensive first-pass metabolism into morphine before crossing the blood-brain barrier; so the effects are the same as orally administered morphine 5,6. Take by injection, diamorphine's acetyl groups facilitate rapid crossing into the brain 5,6. Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups, therefore making it a prodrug for the delivery of morphine 5,6. Subsequently, whether eliciting actions peripherally (on smooth muscle, skeletal muscle, kidney, lung, liver, or spleen tissue 5, for example) or on the central nervous system, it is ultimately the morphine metabolite of heroin that then binds with opioid receptors and produces the narcotic opioid effects commonly associated with the substance 5,6.

Mechanism of action

When administered orally, diamorphine experiences extensive first-pass metabolism by way of deacetylation to generate the active metabolites 6-monoacetylmorphine (6-MAM) and morphine 5,6. Alternatively, when given as an injection the acetyl groups present in the diamorphine/diacetylmorphine compound confer the substance lipophilicity that facilitates diamorphine's rapid crossing of the blood-brain-barrier 5,6. Once in the brain, diamorphine is metabolised via deacetylation to the active 6-MAM and morphine metabolites as well 5,6. Despite diamorphine possessing little to no opioid agonist activity itself, its rapid transit across the blood-brain-barrier elicits a far faster onset of activity in comparison to the extensive first-pass metabolism of oral administration 5,6. Regardless, the metabolism of diamorphine to morphine makes heroin a prodrug for the delivery of morphine 5,6.

Morphine is subsequently 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 1. Morphine, along with other opioids, are agonists to four endogenous neurotransmitters 1. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin 1. The body responds to morphine in the brain by reducing (and sometimes stopping) production of the endogenous opioids when morphine is present 1. 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 morphine besides analgesia (antitussin, anti-diarrheal) 1.

Nevertheless, morphine ultimately elicits the majority of its analgesic activity by binding to mu opioid receptors in both the central and peripheral nervous systems 7. The overall effect of morphine is activation of descending inhibitory pathways of the central nervous system as well as inhibition of nociceptive afferent neurons of the peripheral nervous system, which results in an overall reduction of the nociceptive pain transmission 7.

AMu-type opioid receptor
UKappa-type opioid receptor
UDelta-type opioid receptor
ULiver carboxylesterase 1Not AvailableHumans

Bioavailability is less than 35% when orally administered 2. In particular, some studies have determined that the bioavailability of orally administered diamorphine could be as low as 22.9% (16.4-29.4%) on average in opioid-naive subjects 3.

Nevertheless, diamorphine administered by any many medically indicated routes of administration leads to a rapid absorption 5. Peak serum levels are achieved five to ten minutes subcutaneously, three to five minutes intranasally and intramuscularly, and less than one minute intravenously 5.

Volume of distribution

Data regarding the volume of distribution specific to diamorphine is not readily accessible or available. However, considering diamorphine is considered a prodrug for morphine, the volume of distribution of morphine has been determined to be approximately 1 to 6 L/kg 8.

Protein binding

Diamorphine does not bind to plasma protein 6. However, considering diamorphine is considered a prodrug for morphine, morphine itself is about 20 to 35% reversibly bound to human plasma proteins 6,8.


Once administered into the body, diamorphine undergoes deacetylation via various esterase enzymes to generate active metabolites like 6-monoacetylmorphine and morphine 5,6. In particular, when administered orally, diamorphine undergoes extensive first pass metabolism 5,6.

Hover over products below to view reaction partners

Route of elimination

The majority of the drug is excreted via the kidney as glucuronides and to a much lesser extent as morphine 6. About 7-10 % is eliminated via the biliary system into the faeces 6.


In humans, administered diamorphine has a half-life of approximately two to three minutes 6.


Some studies have determined a relatively high systemic diacetylmorphine clearance of about 8.7 +/- 2.6 L/min, suggesting that the intestine, liver, and blood might all collectively take part in the first pass metabolism of diacetylmorphine to morphine 3, although such clearance observations were made only in opioid-addicted individuals 4.

However, considering diamorphine is considered a prodrug for morphine, the mean adult plasma clearance of morphine is approximately 20 to 30 mL/min/kg 8.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample

Overdosage with diamorphine well characterised by a number of symptoms including respiratory depression, pulmonary oedema, muscle flaccidity, coma or stupor, constricted pupils, cold, clammy skin and occasionally bradycardia and hypotension 5,6. The antidote for heroin overdose or poisoning is naloxone 5.

Heroin Action PathwayDrug action
Heroin Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Diamorphine is combined with 1,2-Benzodiazepine.
AcetazolamideThe risk or severity of CNS depression can be increased when Acetazolamide is combined with Diamorphine.
AcetophenazineThe risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Diamorphine.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Diamorphine.
AgomelatineThe risk or severity of CNS depression can be increased when Diamorphine is combined with Agomelatine.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Diamorphine.
AlimemazineThe risk or severity of hypotension and CNS depression can be increased when Alimemazine is combined with Diamorphine.
AllantoinThe therapeutic efficacy of Allantoin can be decreased when used in combination with Diamorphine.
AlloinThe therapeutic efficacy of Alloin can be decreased when used in combination with Diamorphine.
AlmotriptanThe risk or severity of CNS depression can be increased when Almotriptan is combined with Diamorphine.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
  • Avoid alcohol.


Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Diamorphine hydrochloride8H672SHT8E1502-95-0FZJYQGFGNHGSFX-PVQKIFDLSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Diacetylmorphine HydrochloridePowder, for solution5000 mg / vialIntramuscular; IntravenousPharmascience Inc2022-04-11Not applicableCanada flag
Diacetylmorphine HydrochloridePowder, for solution200 mg / vialIntramuscular; IntravenousPharmascience Inc2022-06-16Not applicableCanada flag
Diamorphine Hydrochloride Inj 100mg/ml BPPowder, for solution100 mg / mLIntramuscular; Intravenous; SubcutaneousTechnilab Pharma Inc.1988-12-311997-08-22Canada flag
Diamorphine Hydrochloride Inj 30mg/ml BPPowder, for solution30 mg / mLIntramuscular; Intravenous; SubcutaneousTechnilab Pharma Inc.1988-12-311997-08-22Canada flag


ATC Codes
N07BC06 — Diamorphine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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.
Organic compounds
Super Class
Alkaloids and derivatives
Sub Class
Not Available
Direct Parent
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
Alkyl aryl ether / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid (CHEBI:27808)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

CAS number
InChI Key
(1S,5R,13R,14S,17R)-10-(acetyloxy)-4-methyl-12-oxa-4-azapentacyclo[^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10,15-tetraen-14-yl acetate


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. [Article]
  2. Rook EJ, van Ree JM, van den Brink W, Hillebrand MJ, Huitema AD, Hendriks VM, Beijnen JH: Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):86-96. doi: 10.1111/j.1742-7843.2006.pto_233.x. [Article]
  3. Halbsguth U, Rentsch KM, Eich-Hochli D, Diterich I, Fattinger K: Oral diacetylmorphine (heroin) yields greater morphine bioavailability than oral morphine: bioavailability related to dosage and prior opioid exposure. Br J Clin Pharmacol. 2008 Dec;66(6):781-91. doi: 10.1111/j.1365-2125.2008.03286.x. [Article]
  4. Rentsch KM, Kullak-Ublick GA, Reichel C, Meier PJ, Fattinger K: Arterial and venous pharmacokinetics of intravenous heroin in subjects who are addicted to narcotics. Clin Pharmacol Ther. 2001 Sep;70(3):237-46. doi: 10.1067/mcp.2001.117981. [Article]
  5. Huecker MR, Marraffa J. Heroin. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan. [Link]
  6. Electronic Medicines Compendium: Diamorphine Hydrochloride BP 100 mg Lyophilisate for Solution for Injection Monograph [Link]
  7. Murphy PB, Barrett MJ. Morphine. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan [Link]
  8. Morphine Sulfate FDA Label [File]
KEGG Compound
PubChem Compound
PubChem Substance
Drugs.com Drug Page
Download (18.8 KB)

Clinical Trials

Clinical Trials
4TerminatedTreatmentSickle Cell Disease (SCD)1
3CompletedBasic ScienceOpioid Related Disorders1
3CompletedTreatmentHeroin Dependence / Opioid Dependence1
3CompletedTreatmentOpiate Addiction1
3CompletedTreatmentOpioid Dependence1
2WithdrawnTreatmentHeroin Dependence / Opioid Related Disorders2
1, 2RecruitingTreatmentOpioid Use Disorder (OUD)1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV) Infections / Opioid Use Disorder (OUD)1
Not AvailableCompletedSupportive CareCancer1


Not Available
Not Available
Dosage Forms
Powder, for solutionIntramuscular; Intravenous200 mg / vial
Powder, for solutionIntramuscular; Intravenous5000 mg / vial
Powder, for solutionIntramuscular; Intravenous; Subcutaneous100 mg / mL
Powder, for solutionIntramuscular; Intravenous; Subcutaneous30 mg / mL
Not Available
Not Available


Experimental Properties
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
Water Solubility0.266 mg/mLALOGPS
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
Polarizability38.19 Å3Chemaxon
Number of Rings5Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
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
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)


Mass Spec (NIST)
Not Available
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


Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Pharmacological action
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
Uniprot ID
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Pharmacological action
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
Uniprot ID
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
  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. [Article]
  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. [Article]
Pharmacological action
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
Uniprot ID
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
  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. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  3. Kieffer BL, Gaveriaux-Ruff C: Exploring the opioid system by gene knockout. Prog Neurobiol. 2002 Apr;66(5):285-306. [Article]
Pharmacological action
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
Uniprot ID
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
  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. [Article]


Pharmacological action
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
Uniprot ID
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
  1. CYTOMEL (liothyronine) FDA label [File]

Drug created at July 31, 2007 13:09 / Updated at November 28, 2023 03:29