Identification

Name
Dihydromorphine
Accession Number
DB01565
Type
Small Molecule
Groups
Experimental, Illicit
Description

A semisynthetic analgesic used in the study of narcotic receptors. It has abuse potential. [PubChem]

Structure
Thumb
Synonyms
Not Available
External IDs
IDS-ND-009 / NSC-117865
Categories
UNII
C3S5FRP6JW
CAS number
509-60-4
Weight
Average: 287.3535
Monoisotopic: 287.152143543
Chemical Formula
C17H21NO3
InChI Key
IJVCSMSMFSCRME-KBQPJGBKSA-N
InChI
InChI=1S/C17H21NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,13,16,19-20H,3,5-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1
IUPAC Name
(1S,5R,13R,14S,17R)-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7(18),8,10-triene-10,14-diol
SMILES
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CCN(C)[C@]([H])(C4)[C@]1([H])CC[C@@H]2O

Pharmacology

Indication

Dihydromorphine is an opioid analgesic used for moderate to severe pain relief.

Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
UDelta-type opioid receptor
agonist
Human
UKappa-type opioid receptor
agonist
Human
UE3 ubiquitin-protein ligase TRIM13
agonist
Human
UPro-opiomelanocortin
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
PathwayCategory
Dihydromorphine Action PathwayDrug action
Dihydromorphine 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 Dihydromorphine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the analgesic activities of Dihydromorphine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the analgesic activities of Dihydromorphine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the analgesic activities of Dihydromorphine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Acetazolamide.
AclidiniumThe risk or severity of adverse effects can be increased when Aclidinium is combined with Dihydromorphine.
Food Interactions
Not Available

References

Synthesis Reference

Herbert Merz, Ingrid Wiedemann, Helmut Ensinger, Klaus Stockhaus, Matthias Grauert, "14-hydroxy-N-(2-methoxyethyl)-7,8-dihydromorphine and -norisomorphine, processes for the preparation thereof and the use thereof as pharmaceutical compositions." U.S. Patent US5240933, issued August 31, 1993.

US5240933
General References
Not Available
External Links
Human Metabolome Database
HMDB0060548
KEGG Compound
C11782
PubChem Compound
5359421
PubChem Substance
46506587
ChemSpider
4514282
BindingDB
50452273
ChEBI
4575
ChEMBL
CHEMBL1500
Wikipedia
Dihydromorphine

Clinical Trials

Clinical Trials
Not Available

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)157 dec °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility1.82 mg/mLALOGPS
logP1.26ALOGPS
logP1.08ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)10.29ChemAxon
pKa (Strongest Basic)9.24ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area52.93 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.16 m3·mol-1ChemAxon
Polarizability30.66 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.995
Blood Brain Barrier+0.985
Caco-2 permeable+0.8356
P-glycoprotein substrateSubstrate0.8896
P-glycoprotein inhibitor INon-inhibitor0.8653
P-glycoprotein inhibitor IINon-inhibitor0.9868
Renal organic cation transporterInhibitor0.5516
CYP450 2C9 substrateNon-substrate0.8115
CYP450 2D6 substrateSubstrate0.8647
CYP450 3A4 substrateSubstrate0.7582
CYP450 1A2 substrateNon-inhibitor0.797
CYP450 2C9 inhibitorNon-inhibitor0.9309
CYP450 2D6 inhibitorNon-inhibitor0.617
CYP450 2C19 inhibitorNon-inhibitor0.7678
CYP450 3A4 inhibitorNon-inhibitor0.8793
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9646
Ames testNon AMES toxic0.7901
CarcinogenicityNon-carcinogens0.9598
BiodegradationNot ready biodegradable0.9846
Rat acute toxicity2.8928 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8927
hERG inhibition (predictor II)Non-inhibitor0.8414
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
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

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 / Aralkylamines / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Trialkylamines / Secondary alcohols / Cyclic alcohols and derivatives
show 4 more
Substituents
Morphinan / Phenanthrene / Tetralin / Coumaran / Alkyl aryl ether / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Piperidine / Benzenoid / Cyclic alcohol
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid (CHEBI:4575)

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. Crooks PA, Kottayil SG, Al-Ghananeem AM, Byrn SR, Butterfield DA: Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4291-5. Epub 2006 Jun 13. [PubMed:16777416]
  2. Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham DJ, Lambert DG: Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile. Br J Anaesth. 2009 Jul;103(1):38-49. doi: 10.1093/bja/aep129. Epub 2009 May 27. [PubMed:19474215]
  3. Gilbert AK, Hosztafi S, Mahurter L, Pasternak GW: Pharmacological characterization of dihydromorphine, 6-acetyldihydromorphine and dihydroheroin analgesia and their differentiation from morphine. Eur J Pharmacol. 2004 May 25;492(2-3):123-30. [PubMed:15178355]
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. Crooks PA, Kottayil SG, Al-Ghananeem AM, Byrn SR, Butterfield DA: Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4291-5. Epub 2006 Jun 13. [PubMed:16777416]
  2. Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham DJ, Lambert DG: Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile. Br J Anaesth. 2009 Jul;103(1):38-49. doi: 10.1093/bja/aep129. Epub 2009 May 27. [PubMed:19474215]
  3. Gilbert AK, Hosztafi S, Mahurter L, Pasternak GW: Pharmacological characterization of dihydromorphine, 6-acetyldihydromorphine and dihydroheroin analgesia and their differentiation from morphine. Eur J Pharmacol. 2004 May 25;492(2-3):123-30. [PubMed:15178355]
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. Crooks PA, Kottayil SG, Al-Ghananeem AM, Byrn SR, Butterfield DA: Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4291-5. Epub 2006 Jun 13. [PubMed:16777416]
  2. Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham DJ, Lambert DG: Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile. Br J Anaesth. 2009 Jul;103(1):38-49. doi: 10.1093/bja/aep129. Epub 2009 May 27. [PubMed:19474215]
  3. Gilbert AK, Hosztafi S, Mahurter L, Pasternak GW: Pharmacological characterization of dihydromorphine, 6-acetyldihydromorphine and dihydroheroin analgesia and their differentiation from morphine. Eur J Pharmacol. 2004 May 25;492(2-3):123-30. [PubMed:15178355]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
E3 ubiquitin ligase involved in the retrotranslocation and turnover of membrane and secretory proteins from the ER through a set of processes named ER-associated degradation (ERAD). This process ac...
Gene Name
TRIM13
Uniprot ID
O60858
Uniprot Name
E3 ubiquitin-protein ligase TRIM13
Molecular Weight
46987.08 Da
References
  1. Liebmann C, Schnittler M, Hartrodt B, Born I, Neubert K: Structure-activity studies of novel casomorphin analogues: binding profiles towards mu 1-, mu 2- and delta -opioid receptors. Pharmazie. 1991 May;46(5):345-8. [PubMed:1654566]
  2. Maneckjee R, Archer S, Zukin RS: Characterization of a polyclonal antibody to the mu opioid receptor. J Neuroimmunol. 1988 Feb;17(3):199-208. [PubMed:2828423]
  3. Ishizuka Y, Oka T: Relation of diltiazem binding sites to opioid receptor subtypes in the guinea-pig brain. Tokai J Exp Clin Med. 1987 Mar;12(1):11-7. [PubMed:2835832]
  4. Koman A, Kolb VM, Terenius L: A naloxone-steroid hybrid azine with selective and long-acting opioid antagonism at delta receptors in vitro. Pharm Res. 1987 Apr;4(2):147-9. [PubMed:2855368]
  5. Ho CL, Hammonds RG Jr, Li CH: Opiate receptor binding profile in the rabbit cerebellum and brain membranes. Biochem Pharmacol. 1985 Apr 1;34(7):925-31. [PubMed:2985086]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Type 4 melanocortin receptor binding
Specific Function
ACTH stimulates the adrenal glands to release cortisol.MSH (melanocyte-stimulating hormone) increases the pigmentation of skin by increasing melanin production in melanocytes.Beta-endorphin and Met...
Gene Name
POMC
Uniprot ID
P01189
Uniprot Name
Pro-opiomelanocortin
Molecular Weight
29423.72 Da
References
  1. Somoza E: Influence of neuroleptics on the binding of met-enkephalin, morphine and dihydromorphine to synaptosome-enriched fractions of rat brain. Neuropharmacology. 1978 Aug;17(8):577-81. [PubMed:29252]
  2. Johnson N, Houghten R, Pasternak GW: Binding of 3H-beta-endorphin in rat brain. Life Sci. 1982 Sep 20-27;31(12-13):1381-4. [PubMed:6292632]

Drug created on July 31, 2007 07:10 / Updated on August 02, 2018 04:38