Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H23N |
Molecular Weight | 277.4033 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CN(C)CCC=C1C2=C(CCC3=C1C=CC=C3)C=CC=C2
InChI
InChIKey=KRMDCWKBEZIMAB-UHFFFAOYSA-N
InChI=1S/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
Molecular Formula | C20H23N |
Molecular Weight | 277.4033 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.rxlist.com/elavil-drug.htm
https://www.ncbi.nlm.nih.gov/pubmed/23235671; https://www.ncbi.nlm.nih.gov/pubmed/11157426; http://www.ncbi.nlm.nih.gov/pubmed/16871467; http://www.ncbi.nlm.nih.gov/pubmed/2578912; http://www.ncbi.nlm.nih.gov/pubmed/?term=15943846
Curator's Comment: description was created based on several sources, including
http://www.rxlist.com/elavil-drug.htm
https://www.ncbi.nlm.nih.gov/pubmed/23235671; https://www.ncbi.nlm.nih.gov/pubmed/11157426; http://www.ncbi.nlm.nih.gov/pubmed/16871467; http://www.ncbi.nlm.nih.gov/pubmed/2578912; http://www.ncbi.nlm.nih.gov/pubmed/?term=15943846
Amitriptyline is a derivative of dibenzocycloheptadiene and a tricyclic antidepressant (TCA) and is mainly used to treat symptoms of depression. It works on the central nervous system (CNS) by inhibiting the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Amitriptyline has been frequently used as an active comparator in clinical trials on newer antidepressants. It is rarely used as a first-line antidepressant nowadays due to its high degree of toxicity in overdose and generally poorer tolerability than the newer antidepressants.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P23975 Gene ID: 6530.0 Gene Symbol: SLC6A2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/14744476 |
3.45 nM [IC50] | ||
Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/14744476 |
13.3 nM [IC50] | ||
Target ID: P28223 Gene ID: 3356.0 Gene Symbol: HTR2A Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/7855217 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Preventing | AMITRIPTYLINE HYDROCHLORIDE Approved UseFor the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states. Launch Date1997 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10383563 |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMITRIPTYLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
593 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10383563 |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMITRIPTYLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
20.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10383563 |
75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMITRIPTYLINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6125396 |
150 mg 1 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
AMITRIPTYLINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 14 uM] | ||||
yes [IC50 6.99 uM] | ||||
yes [IC50 8.8 uM] | ||||
yes [Inhibition 200 uM] | ||||
yes [Ki 31 uM] | ||||
yes [Ki 37.7 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
[Individual conditions of pharmacogenic confusion conditions. Comparison of amitriptyline and clozapine]. | 1976 |
|
Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. | 1999 Aug |
|
[Hypotension refractory to ephedrine after sympathetic blockade in a patient on long-term therapy with tricyclic antidepressants]. | 1999 Oct |
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Gender differences in depression associated with neurologic illness: clinical correlates and pharmacologic response. | 2001 |
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A randomized trial of fluoxetine versus amitriptyline in musculo-skeletal pain. | 2001 |
|
Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans. | 2001 |
|
The concentration of three anti-seizure medications in hair: the effects of hair color, controlling for dose and age. | 2001 |
|
Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants. | 2001 |
|
Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy. | 2001 Apr |
|
The effects of amitriptyline, citalopram and reboxetine on autonomic nervous system. A randomised placebo-controlled study on healthy volunteers. | 2001 Apr |
|
Noradrenergic dysfunction and antidepressant treatment response. | 2001 Apr |
|
[Sensory neuropathy in HIV infection: pathogenesis and therapy]. | 2001 Apr 14 |
|
Controlling phantom limb pain in Sierra Leone. | 2001 Apr 21 |
|
Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates. | 2001 Aug |
|
Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study. | 2001 Feb |
|
Antidepressant treatment and global tests of coagulation and fibrinolysis. | 2001 Feb |
|
Transplacental transfer of amitriptyline and nortriptyline in isolated perfused human placenta. | 2001 Feb |
|
Gabapentin for the treatment of tinnitus: a case report. | 2001 Feb |
|
Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study. | 2001 Feb |
|
Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials. | 2001 Feb |
|
Amitriptyline: still efficacious, but at what cost? | 2001 Feb |
|
Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship. | 2001 Jan |
|
[Non-fatal effect of highly toxic amitriptyline level after suicide attempt. A case report]. | 2001 Jan |
|
Weight outcomes among antidepressant users in nursing facilities. | 2001 Jan |
|
Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na(+) currents in rat sensory neurons. | 2001 Jan |
|
Amitriptyline enhances the central component of physiological tremor. | 2001 Jan |
|
Lamotrigine for central poststroke pain: a randomized controlled trial. | 2001 Jan 23 |
|
Late-onset GM2 gangliosidosis presenting as burning dysesthesias. | 2001 Jul |
|
[Ciguatera: clinical relevance of a marine neurotoxin]. | 2001 Jul 13 |
|
The effect of amitriptyline on pain intensity and perception of stress in bruxers. | 2001 Jun |
|
Assessment of DNA damage in C6 glioma cells after antidepressant treatment using an alkaline comet assay. | 2001 Jun |
|
Ring flexibility within tricyclic antidepressant drugs. | 2001 Jun |
|
Effects of amitriptyline on diurnal variations of oxidation-reduction enzyme activities in rat lymphocytes during experimental desynchronosis. | 2001 May |
|
Treatment of neuropathic pain with venlafaxine. | 2001 May |
|
Advances in the management of neuropathic pain. | 2001 May |
|
Inhibition of synovial plasma extravasation by preemptive administration of an antiinflammatory irrigation solution in the rat knee. | 2001 May |
|
Patterns of response to repeated total sleep deprivations in depression. | 2001 May |
|
Combining psychotherapy and antidepressants in the treatment of depression. | 2001 May |
|
High-performance liquid chromatographic method combining radiochemical and ultraviolet detection for determination of low activities of uridine 5'-diphosphate-glucuronosyltransferase. | 2001 May 15 |
|
Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial. | 2001 May 2 |
|
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor. | 2001 Oct |
|
Efficacy of spinal manipulation for chronic headache: a systematic review. | 2001 Sep |
|
Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye Study. | 2001 Sep |
|
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care. | 2001 Sep 22 |
|
Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. | 2007 May |
|
Intersegmental vessel formation in zebrafish: requirement for VEGF but not BMP signalling revealed by selective and non-selective BMP antagonists. | 2010 Sep |
Sample Use Guides
For outpatients, 75 mg of amitriptyline HCl a day in divided doses. If necessary, this may be increased to a total of 150 mg per day. An alternate method of initiating therapy in outpatients is to begin with 50 to 100 mg amitriptyline HCl at bedtime. This may be increased by 25 or 50 mg as necessary in the bedtime dose to a total of 150 mg per day. Hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary up to 300 mg a day. Not recommended for patients under 12 years of age
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/26504754
Amitriptyline was used at 40 uM in isolated rat hepatocytes for 60,120,180 min.
Substance Class |
Chemical
Created
by
admin
on
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Wed Apr 02 09:57:00 GMT 2025
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Record UNII |
1806D8D52K
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Validated (UNII)
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WHO-ATC |
N06CA01
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WHO-ESSENTIAL MEDICINES LIST |
24.2.1
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FDA ORPHAN DRUG |
288809
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WHO-VATC |
QN06AA09
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LIVERTOX |
NBK548410
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NDF-RT |
N0000175752
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FDA ORPHAN DRUG |
739620
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WHO-ESSENTIAL MEDICINES LIST |
8.4
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NCI_THESAURUS |
C94727
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WHO-VATC |
QN06CA01
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WHO-ATC |
N06AA09
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D000639
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Amitriptyline
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100000092029
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AMITRIPTYLINE
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CHEMBL629
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
Metabolizing reaction by CYP2D6: N-demethylation
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BINDER->LIGAND |
BINDING
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TARGET -> INHIBITOR | |||
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BINDING PROTEIN->LIGAND | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT |
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METABOLIC ENZYME -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
URINE
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METABOLITE ACTIVE -> PARENT |
MAJOR
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METABOLITE -> PARENT |
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METABOLITE -> PARENT |
URINE
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Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
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PARENT -> IMPURITY |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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MAXIMUM TOLERATED DOSE | TOXICITY |
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DEPRESSION, INPATIENTS: 300 MG/DAY |
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Route of Elimination | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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