Page last updated: 2024-12-06

amitriptyline n-oxide

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

Amitriptyline N-oxide is a metabolite of the tricyclic antidepressant amitriptyline. It is formed in the liver by the enzyme cytochrome P450. Amitriptyline N-oxide is pharmacologically inactive and is excreted in the urine. Research on amitriptyline N-oxide has focused on its role in the metabolism of amitriptyline. Studies have shown that the formation of amitriptyline N-oxide is an important pathway for the elimination of amitriptyline from the body. Amitriptyline N-oxide is also being investigated for its potential therapeutic effects. Some studies have suggested that it may have antidepressant activity. However, more research is needed to confirm these findings. Amitriptyline N-oxide is a relatively minor metabolite of amitriptyline, and it is not typically considered to be clinically significant. However, it is important to note that the formation of this metabolite can be affected by factors such as age, liver function, and drug interactions.'

Cross-References

ID SourceID
PubMed CID20313
CHEMBL ID627
CHEBI ID135224
SCHEMBL ID54518
MeSH IDM0049188

Synonyms (58)

Synonym
NSC176555 ,
amitriptyline n-oxide
amitriptylinoxide
NCI60_001463
1-propanamine, 3-(10,11-dihydro-5h-dibenzo(a,d)cyclohepten-5-ylidene)-n,n-dimethyl-n-oxide
equilibrin
10,11-dihydro-n,n-dimethyl-5h-dibenzo(a,d)cycloheptene-delta5,gamma-propylamine-n-oxide
amitriptilinoxido [inn-spanish]
ambivalon
3-(10,11-dihydro-5h-dibenzo(a,d)cyclohepten-5-yliden)-n,n-dimethylpropylamin n-oxid
10,11-dihydro-n,n-dimethyl-5h-dibenzo(a,d)cycloheptene-delta(sup 5,gamma)-propylamine n-oxide
brn 2385442
amitriptylinoxidum [inn-latin]
amitriptylinoxide [inn]
5h-dibenzo(a,d)cycloheptene-delta(sup 5),gamma-propylamine, 10,11-dihydro-n,n-dimethyl-n-oxide
amitriptylinoxyde [inn-french]
(3-(10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5-ylidene)propyl)(hydroxy)dimethyl-5-azane
4317-14-0
D07449
amitriptylinoxide (inn)
3-(5,6-dihydrodibenzo[[?],[?]][7]annulen-11-ylidene)-n,n-dimethyl-propan-1-amine oxide
(3-(10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5-ylidene)propyl)(hydroxy)dimethyl-.lambda.~5~-azane
NCGC00014514
NCI176555
NCISTRUC1_001927
NCISTRUC2_001301
NCGC00097618-01
CHEBI:135224
amitryptyline-n-oxide
j9.621k ,
CHEMBL627
amitriptyline-n-oxide
amitriptyline oxide
10,11-dihydro-n,n-dimethyl-5h-dibenzo(a,d)cycloheptene-delta5,gamma-propylamine n-oxide
CCG-37141
NCGC00014514-02
amitriptylinoxyde
unii-tyr2u59wma
amitriptylinoxidum
amitriptilinoxido
tyr2u59wma ,
bdbm112778
us8629135, sw-03
amitriptylinoxide [mi]
amitriptylinoxide [who-dd]
nortriptyline hydrochloride impurity j [ep impurity]
SCHEMBL54518
5h-dibenzo(a,d)cycloheptene-.delta.5,.gamma.-propylamine, 10,11-dihydro-n,n-dimethyl-n-oxide
3-(10,11-dihydro-5h-dibenzo-[a,d]cyclohepten-5-ylidene)-n,n-dimethyl-1-propanamine n-oxide
ZPMKQFOGINQDAM-UHFFFAOYSA-N
10,11-dihydro-n,n-dimethyl-5h-dibenzo[a,d]cycloheptene-.delta.5,.gamma.-propylamine n-oxide
DTXSID50195758
3-(10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5-ylidene)-n,n-dimethyl-1-propanamine n-oxide
n,n-dimethyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaenylidene)propan-1-amine oxide
amitriptylinoxid
DB13114
Q472476
AKOS040746566

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
"Eleven healthy volunteers were examined in a pharmacokinetic study."( Single oral dose pharmacokinetics of amitriptylinoxide and amitriptyline in humans.
Johannes, KJ; Jungkunz, G; Kuss, HJ, 1985
)
0.27
" In the brain Cmax of AMINO and AMI were similar, whereas in the blood Cmax of AMI was considerably lower than that of the parent compound."( Pharmacokinetics of amitriptyline N-oxide in rats after single and prolonged oral administration.
Danek, L; Melzacka, M, 1983
)
0.59
" The mean plasma half-life and AUC of amitriptyline oxide and its metabolites were significantly higher in patients than in healthy adults."( [Comparative study of the pharmacokinetics of amitriptyline oxide and trimipramine after single administration in healthy male probands and patients with renal failure].
Degen, J; Fischer, W; Höxter, G; Pintar, P; Seiberling, M; Steinhauer, HB; Wölke, E, 1993
)
0.29
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004
)
0.32

Dosage Studied

ExcerptRelevanceReference
" Two groups of 22 patients each received amitriptylinoxide and doxepine respectively at a daily dosage of 120-360 mg for a period of 4 weeks."( A double-blind comparison of amitriptylinoxide versus doxepine in the treatment of severe depression.
Diehl, B; Heinrich, T; König, W, 1994
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
organic tricyclic compound
[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]

Pathways (1)

PathwayProteinsCompounds
Amitriptyline and Nortriptyline Pathway, Pharmacokinetics136

Protein Targets (18)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 2C19 precursorHomo sapiens (human)Potency0.39810.00255.840031.6228AID899
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency1.25890.031610.279239.8107AID884; AID885
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency1.25891.000012.224831.6228AID885
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Ceullar Components (1)

Processvia Protein(s)Taxonomy
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (7)

Assay IDTitleYearJournalArticle
AID8002Observed volume of distribution2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1653791Substrate activity at human mARC1 expressed in Escherichia coli assessed as turnover rates at 3 mM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by UV-Visible spectroscopy based NADH assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID7783Unbound fraction (plasma)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1653806Substrate activity at human mARC2 expressed in Escherichia coli assessed as turnover rates at 3 mM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by LC-MS analysis based assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID1653796Substrate activity at human mARC2 expressed in Escherichia coli assessed as turnover rates at 3 mM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by UV-Visible spectroscopy based NADH assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
AID26380Dissociation constant (pKa)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1653801Substrate activity at human mARC1 expressed in Escherichia coli assessed as turnover rates at 3 mM pre-incubated for 3 mins followed by NADH addition and measured after 15 mins by LC-MS analysis based assay2020Journal of medicinal chemistry, 06-25, Volume: 63, Issue:12
Drug Metabolism by the Mitochondrial Amidoxime Reducing Component (mARC): Rapid Assay and Identification of New Substrates.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (33)

TimeframeStudies, This Drug (%)All Drugs %
pre-199018 (54.55)18.7374
1990's10 (30.30)18.2507
2000's2 (6.06)29.6817
2010's2 (6.06)24.3611
2020's1 (3.03)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.20

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index18.20 (24.57)
Research Supply Index3.85 (2.92)
Research Growth Index4.42 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.20)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials13 (39.39%)5.53%
Reviews1 (3.03%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other19 (57.58%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]