U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H23NO3
Molecular Weight 301.3801
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIHYDROCODEINE

SMILES

[H][C@@]12OC3=C4C(C[C@H]5N(C)CC[C@@]14[C@@]5([H])CC[C@@H]2O)=CC=C3OC

InChI

InChIKey=RBOXVHNMENFORY-DNJOTXNNSA-N
InChI=1S/C18H23NO3/c1-19-8-7-18-11-4-5-13(20)17(18)22-16-14(21-2)6-3-10(15(16)18)9-12(11)19/h3,6,11-13,17,20H,4-5,7-9H2,1-2H3/t11-,12+,13-,17-,18-/m0/s1

HIDE SMILES / InChI

Molecular Formula C18H23NO3
Molecular Weight 301.3801
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including

Dihydrocodeine is an opioid analgesic used as an alternative or adjunct to codeine to treat moderate to severe pain, severe dyspnea, and cough. It is semi-synthetic, and was developed in Germany in 1908 during an international search to find a more effective antitussive agent to help reduce the spread of airborne infectious diseases such as tuburculosis. It was marketed in 1911. Dihydrocodeine is metabolized to dihydromorphine -- a highly active metabolite with a high affinity for mu opioid receptors. Dihydrocodeine is used for the treatment of moderate to severe pain, including post-operative and dental pain. It can also be used to treat chronic pain, breathlessness and coughing. In heroin addicts, dihydrocodeine has been used as a substitute drug, in doses up to 2500mg/day to treat addiction.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.3 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
SYNALGOS-DC

Approved Use

For the relief of moderate to moderately severe pain.

Launch Date

-3.62620813E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
487 pmol/g
60 mg 2 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
341 nM
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
739 nM
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
918 nM
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
60.089 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
18 nM
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.7 nM
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
4.7 pmol/g
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
13 nM
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3367 nM × h
60 mg 2 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
3415 nM × h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
5118 nM × h
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
6566 nM × h
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROCODEINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
301.643 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
132 nM × h
120 mg 1 times / day multiple, oral
dose: 120 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
65 nM × h
60 mg 1 times / day multiple, oral
dose: 60 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
70 nM × h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
99 nM × h
90 mg 1 times / day multiple, oral
dose: 90 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DIHYDROMORPHINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.146 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIHYDROCODEINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
32 mg 6 times / day multiple, oral
Recommended
Dose: 32 mg, 6 times / day
Route: oral
Route: multiple
Dose: 32 mg, 6 times / day
Co-administed with::
aspirin(356.4 mg)
caffeine(30 mg)
Sources:
unhealthy, > 18 years
Health Status: unhealthy
Age Group: > 18 years
Sources:
Other AEs: Respiratory depression...
Other AEs:
Respiratory depression (grade 5)
Sources:
240 mg 2 times / day multiple, oral
Overdose
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Other AEs: Hypercapnic respiratory failure...
Other AEs:
Hypercapnic respiratory failure
Sources:
AEs

AEs

AESignificanceDosePopulation
Respiratory depression grade 5
32 mg 6 times / day multiple, oral
Recommended
Dose: 32 mg, 6 times / day
Route: oral
Route: multiple
Dose: 32 mg, 6 times / day
Co-administed with::
aspirin(356.4 mg)
caffeine(30 mg)
Sources:
unhealthy, > 18 years
Health Status: unhealthy
Age Group: > 18 years
Sources:
Hypercapnic respiratory failure
240 mg 2 times / day multiple, oral
Overdose
Dose: 240 mg, 2 times / day
Route: oral
Route: multiple
Dose: 240 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
PubMed

PubMed

TitleDatePubMed
Postmortem diffusion of drugs from the bladder into femoral venous blood.
2001 Dec 1
Head-column field-amplified sample stacking in presence of siphoning. Application to capillary electrophoresis-electrospray ionization mass spectrometry of opioids in urine.
2001 Jul 27
Important drugs for cough in advanced cancer.
2001 Nov
The role of dihydrocodeine in causing death among drug users in the west of Scotland.
2001 Oct
Novel dynamic polymer coating for capillary electrophoresis in nonaqueous methanolic background electrolytes.
2001 Oct
Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients.
2001 Oct 1
Evaluation and application of liquid chromatographic columns coated with "intelligent" ligands. (III). Immobilized phospholipid column.
2001 Sep
Capillary electrophoresis and capillary electrophoresis-ion trap multiple-stage mass spectrometry for the differentiation and identification of oxycodone and its major metabolites in human urine.
2002 Apr 25
Affinities of dihydrocodeine and its metabolites to opioid receptors.
2002 Aug
[Clinical study of BRON-L syrup (cough suppressant) abuse].
2002 Feb
Diclofenac does not interact with codeine metabolism in vivo: a study in healthy volunteers.
2002 Feb 27
Inhaled pinacidil, an ATP-sensitive K+ channel opener, and moguisteine have potent antitussive effects in guinea pigs.
2002 Jun
A rapid GC-MS method for the determination of dihydrocodeine, codeine, norcodeine, morphine, normorphine and 6-MAM in urine.
2002 Jun 25
Interpretation of GC-MS opiate results in the presence of pholcodine.
2002 Jun 25
Prolonged erections produced by dihydrocodeine and sildenafil.
2002 Jun 29
[Paliative treatment: Treatment of chronic cancer pain (ii): the use of opiates].
2002 May 15
Summary version of the Standards, Options and Recommendations for the use of analgesia for the treatment of nociceptive pain in adults with cancer (update 2002).
2003 Aug
General practice management of illicit drug users in Scotland: a national survey.
2003 Jan
The role of active metabolites in dihydrocodeine effects.
2003 Mar
Effects of second generation of histamine H1 antagonists, cetirizine and ebastine, on the antitussive and rewarding effects of dihydrocodeine in mice.
2003 Mar
Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.
2003 Nov-Dec
Screening and semi-quantitative analysis of post mortem blood for basic drugs using gas chromatography/ion trap mass spectrometry.
2004 Dec 25
Activation of G-proteins by morphine and codeine congeners: insights to the relevance of O- and N-demethylated metabolites at mu- and delta-opioid receptors.
2004 Feb
The Knee Clinical Assessment Study--CAS(K). A prospective study of knee pain and knee osteoarthritis in the general population.
2004 Feb 12
Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens.
2004 Jul 16
ECG abnormalities in co-proxamol (paracetamol/dextropropoxyphene) poisoning.
2005
The role of tramadol in cancer pain treatment--a review.
2005 Jan
Replacement of immunoassay by LC tandem mass spectrometry for the routine measurement of drugs of abuse in oral fluid.
2005 Jul
The effect of non-steroidal anti-inflammatory drugs on medical abortion with mifepristone and misoprostol at 13-22 weeks gestation.
2005 Nov
Hyperinflation and its management in COPD.
2006
Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners.
2006 Aug 15
Treatment of pain during medical abortion.
2006 Jul
Transdermal buprenorphine in the management of persistent pain - safety aspects.
2006 Mar
Validation of the Immunalysis microplate ELISA for the detection of buprenorphine and its metabolite norbuprenorphine in urine.
2006 Mar
Glucuronidation of paracetamol by human liver microsomes in vitro / enzyme kinetic parameters and interactions with short-chain aliphatic alcohols and opiates.
2007
[Transient sick sinus syndrome by oral intake of high dose dehydrocodeine for postherpetic neuralgia].
2007 Apr
Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning.
2007 Apr
Dihydrocodeine as effective as methadone for maintenance of treatment for opiate dependence?
2007 Aug
Deglutition and respiration: development, coordination, and practical implications.
2007 Aug
Distribution of drugs of abuse within specific regions of the human brain.
2007 Aug 6
Patterns in drug use in the United Kingdom as revealed through analysis of hair in a large population sample.
2007 Aug 6
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification.
2007 Jan 8
Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial.
2007 Jan 8
Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs.
2007 Jul 9
The enantiomers of tramadol and its major metabolite inhibit peristalsis in the guinea pig small intestine via differential mechanisms.
2007 Mar 16
"Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1) trials in the UK.
2007 Mar 19
The effect of ethanol on the release of opioids from oral prolonged-release preparations.
2007 Oct
Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry.
2007 Sep
Resolution of secondary amenorrhoea following withdrawal of dihydocodeine.
2008 Apr
[Liposomal boron delivery system for neutron capture therapy].
2008 Feb
Patents

Sample Use Guides

The usual dose of dihydrocodeine is 1 tablet every 4 to 6 hours
Route of Administration: Oral
Dihydrocodeine inhibited paracetamol glucuronidation with Ki value 4.02 mmol/l in human liver microsomes
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:29:26 UTC 2023
Edited
by admin
on Fri Dec 15 16:29:26 UTC 2023
Record UNII
N9I9HDB855
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIHYDROCODEINE
INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
HYDROCODONE HYDROGEN TARTRATE 2.5-HYDRATE IMPURITY B [EP IMPURITY]
Common Name English
DIHYDROCODEINE [MI]
Common Name English
DH-CODEINE
Common Name English
.ALPHA.-HYDROCODOL
Common Name English
DEHACODIN
Common Name English
Dihydrocodeine [WHO-DD]
Common Name English
RAPACODIN
Common Name English
IDS-ND-008(SECT.2)
Code English
NOVICONDIN
Common Name English
3-METHOXY-12-METHYL-5,6,7,7A,8,9-HEXAHYDRO-4AH-8,9C-IMINOETHANOPHENANTHRO(4,5-BCD)FURAN-5-OL
Systematic Name English
dihydrocodeine [INN]
Common Name English
DIHYDROCODEINE [MART.]
Common Name English
REMEDACEN
Brand Name English
4,5.ALPHA.-EPOXY-3-METHOXY-17-METHYLMORPHINAN-6.ALPHA.-OL
Systematic Name English
CODHYDRINE
Common Name English
NSC-231319
Code English
MORPHINAN-6-OL, 4,5-EPOXY-3-METHOXY-17-METHYL-
Systematic Name English
DIHYDROCODEINE [VANDF]
Common Name English
DIHYDRONEOPINE
Common Name English
8,14-DIHYDRONEOPINE
Common Name English
Classification Tree Code System Code
WHO-VATC QN02AA58
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
WHO-ATC N02AA08
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
WHO-VATC QN02AA08
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
WHO-ATC N02AJ02
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
LIVERTOX 308
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
NDF-RT N0000175684
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
DEA NO. 9120
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
NCI_THESAURUS C1506
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
NCI_THESAURUS C67413
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
WHO-ATC N02AA58
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
WHO-ATC N02AJ01
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
WHO-ATC N02AJ03
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
NDF-RT N0000175690
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
Code System Code Type Description
DAILYMED
N9I9HDB855
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
MERCK INDEX
m4459
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY Merck Index
ECHA (EC/EINECS)
204-732-3
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
NSC
231319
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
DRUG CENTRAL
886
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
WIKIPEDIA
DIHYDROCODEINE
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
RXCUI
23088
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY RxNorm
NCI_THESAURUS
C84508
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
IUPHAR
7594
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
ChEMBL
CHEMBL1595
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
CAS
125-28-0
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
FDA UNII
N9I9HDB855
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
PUBCHEM
5284543
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
SMS_ID
100000092218
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
DRUG BANK
DB01551
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
LACTMED
Dihydrocodeine
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
EVMPD
SUB07138MIG
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
INN
728
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
EPA CompTox
DTXSID5022936
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
MESH
C014481
Created by admin on Fri Dec 15 16:29:26 UTC 2023 , Edited by admin on Fri Dec 15 16:29:26 UTC 2023
PRIMARY
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SALT/SOLVATE -> PARENT
APPROXIMATE PURE ANHYDROUS DRUG CONTENT (IN PERCENT)
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