Methadone

Summary

Methadone (CHEMBL651) is an approved small molecule (ATC N02AC52) targeting OPRM1; indicated across 20 conditions including drug dependence and hiv infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02AC52 (+1 more)
• Targets: 1 (OPRM1)
• Indications: 20 conditions
• Clinical trials: 172
• Chemistry: 309.4 Da · C21H27NO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL651
Name	Methadone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4095
ChEBI	CHEBI:167309
ATC	N02AC52, N07BC02
Molecular formula	C21H27NO
Molecular weight	309.4
InChIKey	USSIQXCVUWKGNF-UHFFFAOYSA-N

SMILES: CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2

IUPAC name: 6-(dimethylamino)-4,4-diphenylheptan-3-one

ChEBI definition: A ketone that is heptan-3-one substituted by a dimethylamino group at position 6 and two phenyl groups at position 4.

Also known as: Amidone, Diaminon, Dl-methadone, Dolophin, Heptadone, IDS-NM-002, Metadona, Metasedin, Methadone, Phenadone, Phy, Symoron

Parent form; salt/anhydrous children: CHEMBL1200825

Patent coverage: 12,496 distinct patent families (45,280 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 45,279 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
OPRM1	μ receptor	Agonist	8.39	0%	P35372

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Aldehyde oxidase 1, Voltage-gated L-type calcium channel, D(4) dopamine receptor, Mu-type opioid receptor, D(3) dopamine receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, ATP-dependent translocase ABCB1, Cytochrome P450 2B6.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 12 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRM1	8.39	IC50	4.1	nM	CHEMBL_ACT_125908
OPRM1	7.89	Ki	13	nM	CHEMBL_ACT_24411913
Q9Z0U5	7.52	Ki	30	nM	CHEMBL_ACT_5102820
OPRK1	6.29	IC50	512	nM	CHEMBL_ACT_125909
OPRD1	5.96	IC50	1090	nM	CHEMBL_ACT_125910
DRD3	5.68	Ki	2110	nM	CHEMBL_ACT_24411959
ABCB1	5.12	IC50	7500	nM	CHEMBL_ACT_11001845
KCNH2	5.01	IC50	9772	nM	CHEMBL_ACT_1523708
CYP2B6	5	Ki	10000	nM	CHEMBL_ACT_15453865

Target pathways

Aggregated over 1 target gene(s): OPRM1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1
Peptide ligand-binding receptors	1	OPRM1
G alpha (i) signalling events	1	OPRM1
Interleukin-4 and Interleukin-13 signaling	1	OPRM1
MECP2 regulates neuronal receptors and channels	1	OPRM1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
neuropeptide signaling pathway	1
sensory perception	1
negative regulation of cell population proliferation	1
sensory perception of pain	1
G protein-coupled opioid receptor signaling pathway	1
negative regulation of nitric oxide biosynthetic process	1
behavioral response to ethanol	1
positive regulation of neurogenesis	1
negative regulation of cytosolic calcium ion concentration	1
negative regulation of Wnt protein secretion	1

Indications & clinical

Indications

20 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
drug dependence	4	MONDO:0005303	EFO:0003890
HIV infectious disease	3	MONDO:0005109	EFO:0000764
cocaine dependence	3	MONDO:0005186	EFO:0002610
heroin dependence	3	MONDO:0005367	EFO:0004240
scoliosis	3	MONDO:0005392	EFO:0004273
opiate dependence	3	MONDO:0005530	EFO:0005611
neuralgia	3	MONDO:0021667	EFO:0005762
chronic kidney disease	3	MONDO:0005300	EFO:0003884
neoplasm	3	MONDO:0005070	MONDO:0004992
neonatal abstinence syndrome	2	MONDO:0005566	EFO:0005799
restless legs syndrome	2	MONDO:0005391	EFO:0004270
peripheral neuropathy	2	MONDO:0005244	EFO:0003100
hepatitis C virus infection	1	MONDO:0005231	EFO:0003047

7 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 172.

Phase distribution

Phase	Trials
PHASE4	51
PHASE3	35
Not specified	30
PHASE1	23
PHASE2	19
PHASE1/PHASE2	6
PHASE2/PHASE3	4
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03168958	PHASE4	RECRUITING	Methadone and Quality of Postoperative Recovery
NCT03893734	PHASE4	RECRUITING	Effect of Methadone and Hydromorphone on the QT Interval After Anesthesia and Surgery
NCT06323824	PHASE4	RECRUITING	Office-based Methadone Versus Buprenorphine to Address Retention in Medication for Opioid Use Disorder Treatment.
NCT06525740	PHASE4	RECRUITING	Methadone Versus Intrathecal Hydromorphone for Postoperative Pain Relief in Gynecologic Cancer Undergoing Surgery
NCT06576830	PHASE4	RECRUITING	Optimization of Pediatric Tonsillectomy to IMprove AnaLgesia
NCT06784999	PHASE4	RECRUITING	Sufentanil Infusion vs Intravenous Methadone for Postoperative Analgesia Following Head and Neck Dissection With Free Flap or Rotational Reconstruction
NCT06868589	PHASE4	ACTIVE_NOT_RECRUITING	Reducing Pain With Methadone and Ketamine in Liver Transplant
NCT07222072	PHASE4	RECRUITING	Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study
NCT07485803	PHASE4	NOT_YET_RECRUITING	A RCT Using Methadone in the Management of Post-Operative Pain in Total Knee Replacement
NCT07517679	PHASE4	NOT_YET_RECRUITING	Methadone for Post-operative Spine Surgery
NCT07546396	PHASE4	NOT_YET_RECRUITING	Methadone Rapid Restart
NCT00279565	PHASE4	TERMINATED	Buprenorphine Versus Methadone Maintenance in Hepatitis C Patients Receiving Peg-Intron and Rebetol (Study P04279)(TERMINATED)
NCT00310934	PHASE4	COMPLETED	A Stepwise Strategy Utilizing Buprenorphine and Methadone
NCT00315341	PHASE4	COMPLETED	Starting Treatment With Agonist Replacement Therapies (START)
NCT00879996	PHASE4	COMPLETED	Buprenorphine and Methadone for Opioid Dependent Chronic Pain Patients
NCT00892606	PHASE4	COMPLETED	Methadone Versus Morphine for Orthopedic Surgery Patients
NCT00921843	PHASE4	COMPLETED	Methadone in Pediatric Anesthesia
NCT01047956	PHASE4	UNKNOWN	Compare Methadone Combined With N-Acetyl-Cysteine (NAC) and Methadone Alone for Opioids Astaining
NCT01205516	PHASE4	TERMINATED	Methadone in Neuropathic Pain
NCT01317589	PHASE4	COMPLETED	Treatment of Pain in Head-and-Neck Cancer Patients: is Methadone More Effective?
NCT01542645	PHASE4	COMPLETED	The Effect of Choice of Intraoperative Opioid on Postoperative Pain
NCT01546948	PHASE4	COMPLETED	Intraoperative Opioids and Postoperative Recovery After Hepatobiliary or Foregut Surgery
NCT01559454	PHASE4	COMPLETED	Buprenorphine and Methadone for Opioid-dependent Chronic Back Pain Patients
NCT01723722	PHASE4	COMPLETED	Treatment of Neonatal Abstinence Syndrome
NCT01733693	PHASE4	COMPLETED	Neurocognitive Effects of Opiate Agonist Treatment
NCT01804075	PHASE4	COMPLETED	Comparison Between Methadone and Morphine for Neonatal Opiate Withdrawal
NCT02025855	PHASE4	TERMINATED	Adjunct Methadone to Decrease the Duration of Mechanical Ventilation in the Medical Intensive Care Unit
NCT02107339	PHASE4	COMPLETED	Methadone and Hydromorphone For Spinal Surgery
NCT02206685	PHASE4	COMPLETED	A Trial Comparing Single Intra-op Dose of Methadone Versus Placebo in Patients Undergoing Spine Surgery
NCT02233452	PHASE4	COMPLETED	Methadone and Ketamine for Neuropathic Pain Treatment
NCT02252432	PHASE4	TERMINATED	The Effects of Ketamine and Methadone on Postoperative Pain for Laminectomy
NCT02335398	PHASE4	COMPLETED	Development and Evaluation of a Methadone Protocol for Severe Chronic Pain Management
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02851303	PHASE4	COMPLETED	Morphine Versus Methadone for Opiate Exposed Infants With Neonatal Abstinence Syndrome
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT03033732	PHASE4	COMPLETED	A Pragmatic Randomized Control Trial Comparing Models of Care in the Management of Prescription Opioid Misuse
NCT03045133	PHASE4	COMPLETED	QUALITY OF RECOVERY AFTER INTRAOPERATIVE MORPHINE OR METHADONE
NCT03084588	PHASE4	UNKNOWN	Methadone and Interscalene Block for Shoulder Surgery
NCT03529032	PHASE4	COMPLETED	Preoperative Methadone Single Dose Reduces Postoperative Morphine Consumption.
NCT03726268	PHASE4	COMPLETED	Optimizing Outpatient Anesthesia (OSPREy-Outpatient Surgery Pain Relief Enhancement)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (2) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for methadone, oxycodone and COMT, CYP2D6	CPIC	COMT;CYP2D6;OPRM1
Annotation of CPIC Guideline for methadone and CYP2B6	CPIC	CYP2B6

PharmGKB also curates 100 clinical and 472 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

400 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
ELUXADOLINE	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
MAVORIXAFOR	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	OPRM1
ALFENTANIL	ChEMBL	Phase 4 (approved)	OPRM1
ALOGLIPTIN	ChEMBL	Phase 4 (approved)	OPRM1
ALPIDEM	ChEMBL	Phase 4 (approved)	OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRM1
AMBENONIUM	ChEMBL	Phase 4 (approved)	OPRM1
AMILORIDE	ChEMBL	Phase 4 (approved)	OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRM1
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRM1
AMODIAQUINE	ChEMBL	Phase 4 (approved)	OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRM1
ANTAZOLINE	ChEMBL	Phase 4 (approved)	OPRM1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRM1
ATOMOXETINE	ChEMBL	Phase 4 (approved)	OPRM1
AZELASTINE	ChEMBL	Phase 4 (approved)	OPRM1
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	OPRM1
BENFLUOREX	ChEMBL	Phase 4 (approved)	OPRM1
BENZBROMARONE	ChEMBL	Phase 4 (approved)	OPRM1
BENZIODARONE	ChEMBL	Phase 4 (approved)	OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRM1
BENZYDAMINE	ChEMBL	Phase 4 (approved)	OPRM1
BEPRIDIL	ChEMBL	Phase 4 (approved)	OPRM1
BEXAROTENE	ChEMBL	Phase 4 (approved)	OPRM1
BITHIONOL	ChEMBL	Phase 4 (approved)	OPRM1
BOSUTINIB	ChEMBL	Phase 4 (approved)	OPRM1
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	OPRM1
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	OPRM1
BROMPERIDOL	ChEMBL	Phase 4 (approved)	OPRM1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRM1
CARVEDILOL	ChEMBL	Phase 4 (approved)	OPRM1
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	OPRM1
CETRORELIX	ChEMBL	Phase 4 (approved)	OPRM1
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRM1
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	OPRM1
CINACALCET	ChEMBL	Phase 4 (approved)	OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRM1
CITALOPRAM	ChEMBL	Phase 4 (approved)	OPRM1
CLEMASTINE	ChEMBL	Phase 4 (approved)	OPRM1
CLOMIPHENE	ChEMBL	Phase 4 (approved)	OPRM1
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	OPRM1
CLOPIDOGREL	ChEMBL	Phase 4 (approved)	OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRM1
COBIMETINIB	ChEMBL	Phase 4 (approved)	OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRM1
CYCLIZINE	ChEMBL	Phase 4 (approved)	OPRM1
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	OPRM1
DANAZOL	ChEMBL	Phase 4 (approved)	OPRM1