DIHYDROCODEINE

US Previously Marketed

First approved in 1956

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 Search

SMILES

COC1=C2O[C@H]3[C@@H](O)CC[C@H]4[C@H]5CC(C=C1)=C2[C@@]34CCN5C

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
Sources: http://www.drugbank.ca/drugs/DB01551
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Mu opioid receptor 231 Target ID: CHEMBL233 Sources: http://www.genome.jp/dbget-bin/www_bget?D07831	Agonist 2752		0.3 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 619 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/011483s027lbl.pdf	Palliative		Approved 8583	SYNALGOS-DC Approved Use For the relief of moderate to moderately severe pain. Launch Date 1958

C_max

Value	Dose	Analyte	Population
487 pmol/g EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
4.7 pmol/g EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
341 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
8.7 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
739 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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 EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
18 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
13 nM EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
60.089 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885392/	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

AUC

Value	Dose	Analyte	Population
3367 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
70 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
3415 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
65 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
5118 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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 EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
132 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
99 nM × h EXPERIMENT https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1365-2125.1999.00042.x	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
301.643 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885392/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.146 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885392/	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

Dose	Population	Adverse 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf	unhealthy, > 18 years Health Status: unhealthy Age Group: > 18 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf	Other AEs: Respiratory depression... Other AEs: Respiratory depression (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/26479786	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26479786	Other AEs: Hypercapnic respiratory failure... Other AEs: Hypercapnic respiratory failure Sources: https://pubmed.ncbi.nlm.nih.gov/26479786

AEs

AE	Significance	Dose	Population
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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf	unhealthy, > 18 years Health Status: unhealthy Age Group: > 18 years Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/011483s033lbl.pdf
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: https://pubmed.ncbi.nlm.nih.gov/26479786	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/26479786

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1197 CYP2A6 626 CYP2C19 1119 UGT2B7 456

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2A6 626	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2C19 1119	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2C9 1193	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	likely
CYP2D6 1388	substrate 4014 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042888/pdf/bcp_0626.pdf#page=5 Page: 5.0	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14597688/ Page: 3.0	yes
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/14597688/ Page: 3.0	yes

Sourcing

Vendor/Aggregator	ID	URL
BioSynth	D-3270
Compound Cloud	46174078
Compound Cloud	5284543
Compound Cloud	5492624
Compound Cloud	5493302
eMolecules	303498464
NovoSeek	5284543
Parchem	56756	https://www.parchem.com/chemical-supplier-distributor/Pseudomorphine-056756.aspx
Sigma Aldrich	D-019
Sigma Aldrich	D-019\|CERILLIAN
Smolecule	S526105	http://www.smolecule.com/products/s526105
Tetrahedron	TS81021
THE BioTek	bt-264832	https://www.thebiotek.com/product/inhibitors/bt-264832
Toronto Research Chemicals	KIT2290
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-0343A
ZINC	ZINC000004215736	http://zinc15.docking.org/substances/ZINC000004215736

PubMed

Title	Date	PubMed
Postmortem diffusion of drugs from the bladder into femoral venous blood.	2001 Dec 1	11728758
Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK-PD modelling analysis.	2001 Jul	11453888
Myocardial Infarction associated with methadone and/or dihydrocodeine.	2001 Mar	11316924
Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects.	2001 Mar	11240075
Dihydrocodeine--drug of use or misuse?	2001 May	11360709
Important drugs for cough in advanced cancer.	2001 Nov	11762966
The role of dihydrocodeine in causing death among drug users in the west of Scotland.	2001 Oct	11771494
Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients.	2001 Oct 1	11543987
Affinities of dihydrocodeine and its metabolites to opioid receptors.	2002 Aug	12420793
[Clinical study of BRON-L syrup (cough suppressant) abuse].	2002 Feb	11915306
Inhaled pinacidil, an ATP-sensitive K+ channel opener, and moguisteine have potent antitussive effects in guinea pigs.	2002 Jun	12120760
Alcohol consumption in heroin users, methadone-substituted and codeine-substituted patients--frequency and correlates of use.	2003 Jan	12566797
General practice management of illicit drug users in Scotland: a national survey.	2003 Jan	12492763
The role of active metabolites in dihydrocodeine effects.	2003 Mar	12665158
Development of a directly compressible poly(ethylene oxide) matrix for the sustained-release of dihydrocodeine bitartrate.	2003 Nov	14677766
Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.	2003 Nov-Dec	14597688
Putting an Ecstasy test kit to the test: harm reduction or harm induction?	2003 Oct	14594341
The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project: an open-label pragmatic randomised control trial comparing the efficacy of differing therapeutic agents for primary care detoxification from either street heroin or methadone [ISRCTN07752728].	2004 Apr 29	15117415
Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens.	2004 Jul 16	15240036
Replacement of immunoassay by LC tandem mass spectrometry for the routine measurement of drugs of abuse in oral fluid.	2005 Jul	15989728
The prescribing of methadone and other opioids to addicts: national survey of GPs in England and Wales.	2005 Jun	15970068
Hyperinflation and its management in COPD.	2006	18044095
Addressing the efficacy of dihydrocodeine versus methadone as an alternative maintenance treatment for opiate dependence: A randomized controlled trial.	2006 Dec	17156174
Patterns in drug use in the United Kingdom as revealed through analysis of hair in a large population sample.	2007 Aug 6	17614228
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	17210080
Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.	2008 Apr 11	18405372
Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002-2005.	2008 May 6	18460194

Patents

Sample Use Guides

In Vivo Use Guide

The usual dose of dihydrocodeine is 1 tablet every 4 to 6 hours

Route of Administration: Oral

In Vitro Use Guide

Dihydrocodeine inhibited paracetamol glucuronidation with Ki value 4.02 mmol/l in human liver microsomes

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:29:25 GMT 2025` Edited by `admin` on `Mon Mar 31 18:29:25 GMT 2025`
Record UNII	N9I9HDB855
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

REMEDACEN

Preferred Name

English

DIHYDROCODEINE

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

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