Page last updated: 2024-12-09

dextromethadone

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

D-methadone: an NMDA receptor antagonist analgesic that lacks opioid activity [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

dextromethadone : A 6-(dimethylamino)-4,4-diphenylheptan-3-one that has (S)-configuration. It is the less active enantiomer of methadone and has very little activity on opioid receptors and mainly responsible for the inhibition of hERG K+ channels and thus for cardiac toxicity. The drug is currently under clinical development for the treatment of major depressive disorder. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID643985
CHEMBL ID350719
CHEBI ID167308
SCHEMBL ID24294

Synonyms (43)

Synonym
(+)-(s)-6-(dimethylamino)-4,4-diphenyl-3-heptanone
rel-1017
(6s)-6-(dimethylamino)-4,4-diphenylheptan-3-one
(s)-methadone
CHEBI:167308
3-heptanone, 6-(dimethylamino)-4,4-diphenyl-, (s)-
brn 3213667
(s)-6-(dimethylamino)-4,4-diphenyl-3-heptanone
3-heptanone, 6-(dimethylamino)-4,4-diphenyl-, (6s)- (9ci)
3-heptanone, 6-(dimethylamino)-4,4-diphenyl-, (6s)-
d-6-(dimethylamino)-4,4-diphenyl-3-heptanone
(6s)-methadone
3-heptanone, 6-(dimethylamino)-4,4-diphenyl-, (s)- (8ci)
l-(+)-methadone
s-(+)-methadone
(+)-(s)-methadone
methadone, (+)-
5653-80-5
d-methadone
6s-methadone
(+)-(6s)-methadone
(+)-methadone
(s)-(+)-methadone
dextromethadone
s-methadone
CHEMBL350719 ,
esmethadone
unii-s95rzh8amh
esmethadone [usan]
3-14-00-00279 (beilstein handbook reference)
s95rzh8amh ,
who 11978
SCHEMBL24294
(s)-6-dimethylamino4,4-diphenylheptan-3-on
DB15198
esmethadone [inn]
(6s)-6-(dimethylamino)-4,4-diphenyl-3-heptanone
dextromethadone [ep impurity]
bdbm50223640
Q15634047
SB18896
(s)-6-(dimethylamino)-4,4-diphenylheptan-3-one
DTXSID501045751

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Single doses up to 150 mg and daily doses up to 75 mg for 10 days were well tolerated with mostly mild treatment-emergent adverse events and no severe or serious adverse events."( Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects: Results of Two Phase 1 Studies.
Bernstein, G; Davis, K; Inturrisi, C; Manfredi, PL; McDonnell, M; Mills, C; Oldenhof, J; Vitolo, OV; Wang, L,
)
0.13

Pharmacokinetics

ExcerptReferenceRelevance
"This trial was aimed to estimate the pharmacokinetic interaction between voriconazole and methadone at steady state in male patients on methadone therapy and to characterize the safety and tolerability profile during the coadministration."( Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
Foster, G; Labadie, R; Liu, P; Sharma, A; Somoza, E, 2007
)
0.34
"We conducted 2 phase 1, double-blind, randomized, placebo-controlled, single- and multiple-ascending-dose studies to investigate the safety and tolerability of oral D-methadone and to characterize its pharmacokinetic profile in healthy opioid-naive volunteers."( Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects: Results of Two Phase 1 Studies.
Bernstein, G; Davis, K; Inturrisi, C; Manfredi, PL; McDonnell, M; Mills, C; Oldenhof, J; Vitolo, OV; Wang, L,
)
0.13

Bioavailability

ExcerptReferenceRelevance
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."( Hologram QSAR model for the prediction of human oral bioavailability.
Andricopulo, AD; Moda, TL; Montanari, CA, 2007
)
0.34

Dosage Studied

ExcerptRelevanceReference
" An overall dose-response effect was observed, with higher doses resulting in larger QTcF (QT interval corrected using Fridericia formula) changes from baseline, but none of the changes were considered clinically significant by the investigators."( Characterization of the Safety and Pharmacokinetic Profile of D-Methadone, a Novel N-Methyl-D-Aspartate Receptor Antagonist in Healthy, Opioid-Naive Subjects: Results of Two Phase 1 Studies.
Bernstein, G; Davis, K; Inturrisi, C; Manfredi, PL; McDonnell, M; Mills, C; Oldenhof, J; Vitolo, OV; Wang, L,
)
0.13
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
NMDA receptor antagonistAny substance that inhibits the action of N-methyl-D-aspartate (NMDA) receptors. They tend to induce a state known as dissociative anesthesia, marked by catalepsy, amnesia, and analgesia, while side effects can include hallucinations, nightmares, and confusion. Due to their psychotomimetic effects, many NMDA receptor antagonists are used as recreational drugs.
opioid analgesicA narcotic or opioid substance, synthetic or semisynthetic agent producing profound analgesia, drowsiness, and changes in mood.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
6-(dimethylamino)-4,4-diphenylheptan-3-oneA ketone that is heptan-3-one substituted by a dimethylamino group at position 6 and two phenyl groups at position 4.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (14)

Assay IDTitleYearJournalArticle
AID148466Evaluated for analgesic activity as effective dose1982Journal of medicinal chemistry, Jun, Volume: 25, Issue:6
Conformation-activity study of methadone and related compounds.
AID278721AUC (0-24h) in opiate abstinence syndrome patient at 30 to 100 mg, po QD after 2 days2007Antimicrobial agents and chemotherapy, Jan, Volume: 51, Issue:1
Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
AID278719Dose normalized Cmax in opiate abstinence syndrome patient at 30 to 100 mg, po QD after 2 days2007Antimicrobial agents and chemotherapy, Jan, Volume: 51, Issue:1
Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
AID228952Molar potency (1/IC50) in the guinea pig ileum divided by its potency in the mouse vas deferens.1982Journal of medicinal chemistry, Jun, Volume: 25, Issue:6
Synthesis, X-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that mu and delta opioid receptors possess different stereochemical requirements.
AID148886In vitro relative molar potency represents the morphine ED50 (12.4 pmol/kg)/compound ED50 towards opioid receptor using the hotplate procedure in mice1982Journal of medicinal chemistry, Jun, Volume: 25, Issue:6
Synthesis, X-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that mu and delta opioid receptors possess different stereochemical requirements.
AID278718Dose normalized AUC (0-24h) in opiate abstinence syndrome patient at 30 to 100 mg, po QD after 2 days2007Antimicrobial agents and chemotherapy, Jan, Volume: 51, Issue:1
Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
AID278723Cmin in opiate abstinence syndrome patient at 30 to 100 mg, po QD after 2 days2007Antimicrobial agents and chemotherapy, Jan, Volume: 51, Issue:1
Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
AID278722Cmax in opiate abstinence syndrome patient at 30 to 100 mg, po QD after 2 days2007Antimicrobial agents and chemotherapy, Jan, Volume: 51, Issue:1
Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
AID148889In vitro relative potency towards opioid receptor to morphine (IC50, 4.4E-8M) in mouse vas deferens was determined1982Journal of medicinal chemistry, Jun, Volume: 25, Issue:6
Synthesis, X-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that mu and delta opioid receptors possess different stereochemical requirements.
AID278720Dose normalized Tmax in opiate abstinence syndrome patient at 30 to 100 mg, po QD after 2 days2007Antimicrobial agents and chemotherapy, Jan, Volume: 51, Issue:1
Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.
AID148607In vitro relative potency towards opioid receptor to morphine (IC50, 6.8E-8M) in guinea pig ileum was determined1982Journal of medicinal chemistry, Jun, Volume: 25, Issue:6
Synthesis, X-ray crystallographic determination, and opioid activity of erythro-5-methylmethadone enantiomers. Evidence which suggests that mu and delta opioid receptors possess different stereochemical requirements.
AID150402Compound was evaluated for the inhibition of [3H]- naloxone binding to Opioid receptors in rat brain membrane in the presence of Na1981Journal of medicinal chemistry, Jul, Volume: 24, Issue:7
Synthesis of analogues of acetylmethadol and methadol as potential narcotic antagonists.
AID311524Oral bioavailability in human2007Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24
Hologram QSAR model for the prediction of human oral bioavailability.
AID150401Inhibition of [3H]- naloxone binding to Opioid receptors in rat brain membrane in the absence of Na1981Journal of medicinal chemistry, Jul, Volume: 24, Issue:7
Synthesis of analogues of acetylmethadol and methadol as potential narcotic antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (9)

TimeframeStudies, This Drug (%)All Drugs %
pre-19903 (33.33)18.7374
1990's0 (0.00)18.2507
2000's2 (22.22)29.6817
2010's2 (22.22)24.3611
2020's2 (22.22)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (20.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other8 (80.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]