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

Details

Stereochemistry RACEMIC
Molecular Formula C21H27NO.ClH
Molecular Weight 345.906
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHADONE HYDROCHLORIDE

SMILES

Cl.CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2

InChI

InChIKey=FJQXCDYVZAHXNS-UHFFFAOYSA-N
InChI=1S/C21H27NO.ClH/c1-5-20(23)21(16-17(2)22(3)4,18-12-8-6-9-13-18)19-14-10-7-11-15-19;/h6-15,17H,5,16H2,1-4H3;1H

HIDE SMILES / InChI

Molecular Formula C21H27NO
Molecular Weight 309.4452
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/006134s040s041lbl.pdf | https://www.drugs.com/pro/diskets.html

Methadone, sold under the brand names Dolophine among others, is an synthetic opioid that is used as the hydrochloride to treat pain and as maintenance therapy or to help with detoxification in people with opioid dependence. Methadone hydrochloride is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine. Some data also indicate that methadone acts as an antagonist at the NMDA-receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown. Most common adverse reactions are: lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. Avoid use mixed agonist/antagonist and partial agonist opioid analgesics with DOLOPHINE because they may reduce analgesic effect of DOLOPHINE or precipitate withdrawal symptoms.

CNS Activity

Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/5084666

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.51 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
DOLOPHINE HYDROCHLORIDE

Approved Use

For the treatment of moderate to severe pain not responsive to non-narcotic analgesics. For detoxification treatment of opioid addiction (heroin or other morphine-like drugs). For maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services. Note – Outpatient maintenance and outpatient detoxification treatment may be provided only by Opioid Treatment Programs (OTPs) certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA). This does not preclude the maintenance treatment of a patient with concurrent opioid addiction who is hospitalized for conditions other than opioid addiction and who requires temporary maintenance during the critical period of his/her stay, or of a patient whose enrollment has been verified in a program which has been certified for maintenance treatment with methadone.

Launch Date

-7.0649283E11
Palliative
DOLOPHINE HYDROCHLORIDE

Approved Use

For the treatment of moderate to severe pain not responsive to non-narcotic analgesics. For detoxification treatment of opioid addiction (heroin or other morphine-like drugs). For maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services. Note – Outpatient maintenance and outpatient detoxification treatment may be provided only by Opioid Treatment Programs (OTPs) certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA). This does not preclude the maintenance treatment of a patient with concurrent opioid addiction who is hospitalized for conditions other than opioid addiction and who requires temporary maintenance during the critical period of his/her stay, or of a patient whose enrollment has been verified in a program which has been certified for maintenance treatment with methadone.

Launch Date

-7.0649283E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
548 ng/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
METHADONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
494 ng/mL
70 mg 1 times / day steady-state, oral
dose: 70 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
METHADONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
40.2 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHADONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
54 ng/mL
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
8.54 mg × h/L
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
METHADONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
8.27 μg × h/mL
70 mg 1 times / day steady-state, oral
dose: 70 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
METHADONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1073 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHADONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.61 mg × h/L
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
31.2 h
60 mg 1 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
METHADONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
39 h
70 mg 1 times / day steady-state, oral
dose: 70 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
METHADONE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
39.3 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
METHADONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
10 mg 3 times / day multiple, intravenous (starting)
Recommended
Dose: 10 mg, 3 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
Other AEs: Withdrawal syndrome neonatal...
10 mg 3 times / day multiple, intravenous (starting)
Recommended
Dose: 10 mg, 3 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
unhealthy, adult
Other AEs: Respiratory depression, Addiction...
Other AEs:
Respiratory depression (grade 5)
Addiction
QT interval prolonged (grade 5)
Sources:
20 mg single, oral (starting)
Recommended
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, adult
Other AEs: Respiratory depression, QT interval prolonged...
Other AEs:
Respiratory depression (grade 5)
QT interval prolonged
Arrhythmia (serious)
Sources:
AEs

AEs

AESignificanceDosePopulation
Withdrawal syndrome neonatal
10 mg 3 times / day multiple, intravenous (starting)
Recommended
Dose: 10 mg, 3 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
pregnant, adult
Health Status: pregnant
Age Group: adult
Sex: F
Sources:
Addiction
10 mg 3 times / day multiple, intravenous (starting)
Recommended
Dose: 10 mg, 3 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
unhealthy, adult
QT interval prolonged grade 5
10 mg 3 times / day multiple, intravenous (starting)
Recommended
Dose: 10 mg, 3 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
unhealthy, adult
Respiratory depression grade 5
10 mg 3 times / day multiple, intravenous (starting)
Recommended
Dose: 10 mg, 3 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 3 times / day
Sources:
unhealthy, adult
QT interval prolonged
20 mg single, oral (starting)
Recommended
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, adult
Respiratory depression grade 5
20 mg single, oral (starting)
Recommended
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, adult
Arrhythmia serious
20 mg single, oral (starting)
Recommended
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, adult
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
yes
yes
yes (co-administration study)
Comment: CYP450 inducers: concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms; phenytoin administration resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. CYP450 inhibitors: Repeat dose administration of oral voriconazole increased the peak plasma concentration (Cmax) and AUC of (R)-methadone by 31% and 47%, respectively, in subjects receiving a methadone maintenance dose. The Cmax and AUC of (S)-methadone increased by 65% and 103%, respectively
Page: 29.0
yes
yes (co-administration study)
Comment: CYP450 inducers: concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms; phenytoin administration resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. CYP450 inhibitors: Repeat dose administration of oral voriconazole increased the peak plasma concentration (Cmax) and AUC of (R)-methadone by 31% and 47%, respectively, in subjects receiving a methadone maintenance dose. The Cmax and AUC of (S)-methadone increased by 65% and 103%, respectively
Page: 29.0
yes
yes (co-administration study)
Comment: CYP450 inducers: concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms; phenytoin administration resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. CYP450 inhibitors: Repeat dose administration of oral voriconazole increased the peak plasma concentration (Cmax) and AUC of (R)-methadone by 31% and 47%, respectively, in subjects receiving a methadone maintenance dose. The Cmax and AUC of (S)-methadone increased by 65% and 103%, respectively
Page: 29.0
yes
yes (co-administration study)
Comment: CYP450 inducers: concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms; phenytoin administration resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. CYP450 inhibitors: Repeat dose administration of oral voriconazole increased the peak plasma concentration (Cmax) and AUC of (R)-methadone by 31% and 47%, respectively, in subjects receiving a methadone maintenance dose. The Cmax and AUC of (S)-methadone increased by 65% and 103%, respectively
Page: 29.0
yes
yes (co-administration study)
Comment: CYP450 inducers: concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms; phenytoin administration resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. CYP450 inhibitors: Repeat dose administration of oral voriconazole increased the peak plasma concentration (Cmax) and AUC of (R)-methadone by 31% and 47%, respectively, in subjects receiving a methadone maintenance dose. The Cmax and AUC of (S)-methadone increased by 65% and 103%, respectively
Page: 29.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[Methadone withdrawal syndrome induced by nevirapine].
2000 Mar 18
[Postpartum risk factors in the development of children born to opiate-addicted mothers; comparison between mothers with and without methadone substitution].
2000 Sep
Intravenous clonidine use in a neonate experiencing opioid-induced myoclonus.
2001 Aug
Family history influence on drug abuse severity and treatment outcome.
2001 Feb 1
Bile duct dilation with chronic methadone use in asymptomatic patients: ERCP findings in 6 patients.
2003 Jul
The impact of methadone induction on cardiac conduction in opiate users.
2003 Jul 15
Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes.
2003 Jun
Methadone treatment induces attenuation of cerebrovascular deficits associated with the prolonged abuse of cocaine and heroin.
2003 Mar
Safety of injectable opioid maintenance treatment for heroin dependence.
2003 Oct 15
Methadone metabolism by human placenta.
2004 Aug 1
Obsessive-compulsive symptoms precipitated by methadone tapering.
2004 Dec
The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone.
2004 May
Agonist-like or antagonist-like treatment for cocaine dependence with methadone for heroin dependence: two double-blind randomized clinical trials.
2004 May
[Preclinical management of accidental methadone intoxication of a 4-year-old girl. Antagonist or intubation?].
2004 Oct
QT prolongation and syncope with methadone, doxepin, and a beta-blocker.
2005 Oct
Methadone treatment of chronic non-malignant pain and opioid dependence--a long-term follow-up.
2006 Apr
Variables associated with perceived sleep disorders in methadone maintenance treatment (MMT) patients.
2006 Apr 28
Patents

Sample Use Guides

Chronic pain: oral initial dose - 2.5 mg every 8 to 12 hours; Intravenous initial dose: 2.5 mg to 10 mg every 8 to 12 hours Opiate withdrawal: Initial dose - 20 to 30 mg orally; an additional 5 to 10 mg may be given orally after 2 to 4 hours if withdrawal symptoms have not been suppressed or if symptoms reappear. -Maximum initial dose: 30 mg -Maximum day 1 dose: 40 mg
Route of Administration: Other
In the presence of 1 uM methadone, the maximum 86Rb+ efflux stimulated by nicotine (Emax) was markedly reduced, but the EC50 for nicotine was altered only slightly, if at all.
Substance Class Chemical
Created
by admin
on Fri Dec 16 16:32:18 UTC 2022
Edited
by admin
on Fri Dec 16 16:32:18 UTC 2022
Record UNII
229809935B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METHADONE HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   VANDF   WHO-DD  
Common Name English
METHADONE HYDROCHLORIDE CII [USP-RS]
Common Name English
METHADONE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
METHADONE HYDROCHLORIDE [JAN]
Common Name English
4,4-DIPHENYL-6-DIMETHYLAMINO-3-HEPTANONE HYDROCHLORIDE
Systematic Name English
6-(Dimethylamino)-4,4-diphenyl-3-heptanone hydrochloride
Systematic Name English
Methadone hydrochloride [WHO-DD]
Common Name English
METHADONE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
3-HEPTANONE, 6-(DIMETHYLAMINO)-4,4-DIPHENYL-, HYDROCHLORIDE
Systematic Name English
DL-6-DIMETHYLAMINO-4,4-DIPHENYL-3-HEPTANONE HYDROCHLORIDE
Common Name English
FENADONE
Brand Name English
METHADONE HYDROCHLORIDE [MI]
Common Name English
BUTALGIN
Brand Name English
METHADOSE
Brand Name English
METHADONE HYDROCHLORIDE CII
USP-RS  
Common Name English
AN-148
Code English
METHADONE HYDROCHLORIDE [USP-RS]
Common Name English
DOLOPHINE HYDROCHLORIDE
Brand Name English
MECODIN
Brand Name English
PHENADONE HYDROCHLORIDE
Common Name English
NSC-19600
Code English
HEPTADON
Brand Name English
METHADONE HCL
Common Name English
METHADONE HYDROCHLORIDE [EP IMPURITY]
Common Name English
METHADONE HYDROCHLORIDE [VANDF]
Common Name English
METHADONE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
WESTADONE
Brand Name English
3-HEPTANONE, 6-(DIMETHYLAMINO)-4,4-DIPHENYL-, HYDROCHLORIDE (1:1)
Systematic Name English
KETALGIN HYDROCHLORIDE
Brand Name English
ADANON HYDROCHLORIDE
Brand Name English
DOLOPHINE
Brand Name English
DOLOFIN HYDROCHLORIDE
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C1506
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
DEA NO. 9250
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
NCI_THESAURUS C67413
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
Code System Code Type Description
ChEMBL
CHEMBL651
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
PUBCHEM
14184
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
RXCUI
218337
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY RxNorm
CAS
70181-39-4
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
SUPERSEDED
DRUG BANK
DBSALT000346
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
CAS
70172-45-1
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
SUPERSEDED
EPA CompTox
DTXSID2020501
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
CAS
1095-90-5
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
ECHA (EC/EINECS)
214-140-7
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
DAILYMED
229809935B
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
NSC
19600
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
FDA UNII
229809935B
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
EVMPD
SUB03203MIG
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
CHEBI
50140
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
RS_ITEM_NUM
1398009
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
CAS
125-56-4
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
SUPERSEDED
MERCK INDEX
M7286
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY Merck Index
NCI_THESAURUS
C638
Created by admin on Fri Dec 16 16:32:19 UTC 2022 , Edited by admin on Fri Dec 16 16:32:19 UTC 2022
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
USP
Related Record Type Details
METABOLITE INACTIVE -> PARENT
Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9 and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine.
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (GC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (GC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (GC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (GC)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (GC)
EP
Related Record Type Details
ACTIVE MOIETY