U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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
Structure of Amitriptyline

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

HIDE SMILES / InChI

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

Description
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.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P23975
Gene ID: 6530.0
Gene Symbol: SLC6A2
Target Organism: Homo sapiens (Human)
3.45 nM [IC50]
Target ID: P31645
Gene ID: 6532.0
Gene Symbol: SLC6A4
Target Organism: Homo sapiens (Human)
13.3 nM [IC50]
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
AMITRIPTYLINE HYDROCHLORIDE

Approved Use

For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.

Launch Date

1997
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.3 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
593 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
20.4 h
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

Funbound

ValueDoseCo-administeredAnalytePopulation
7.7%
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

OverviewOther

Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[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
Gender differences in depression associated with neurologic illness: clinical correlates and pharmacologic response.
2001
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
Patents

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
Amitriptyline was used at 40 uM in isolated rat hepatocytes for 60,120,180 min.
Substance Class Chemical
Created
by admin
on Wed Apr 02 09:57:00 GMT 2025
Edited
by admin
on Wed Apr 02 09:57:00 GMT 2025
Record UNII
1806D8D52K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LAROXYL
Preferred Name English
Amitriptyline
INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
1-PROPANAMINE, 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N,N-DIMETHYL-
Systematic Name English
3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N,N-DIMETHYL-1-PROPANAMINE
Systematic Name English
AMITRIPTYLINE [USP IMPURITY]
Common Name English
AMITRIPTYLINE [MI]
Common Name English
AMITRIPTYLINE [VANDF]
Common Name English
amitriptyline [INN]
Common Name English
NORTRIPTYLINE HYDROCHLORIDE IMPURITY F [EP IMPURITY]
Common Name English
Amitriptyline [WHO-DD]
Common Name English
AMITRIPTYLINE [MART.]
Common Name English
SEROTEN
Common Name English
PROHEPTADIENE
Common Name English
TRIPTANOL
Common Name English
DAMITRIPTYLINE
Common Name English
FLAVYL
Common Name English
Classification Tree Code System Code
WHO-ATC N06CA01
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
WHO-ESSENTIAL MEDICINES LIST 24.2.1
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
FDA ORPHAN DRUG 288809
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
WHO-VATC QN06AA09
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
LIVERTOX NBK548410
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
NDF-RT N0000175752
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
FDA ORPHAN DRUG 739620
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
WHO-ESSENTIAL MEDICINES LIST 8.4
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
NCI_THESAURUS C94727
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
WHO-VATC QN06CA01
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
WHO-ATC N06AA09
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
Code System Code Type Description
MESH
D000639
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
LACTMED
Amitriptyline
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
SMS_ID
100000092029
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
WIKIPEDIA
AMITRIPTYLINE
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
HSDB
3007
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
INN
976
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
PUBCHEM
2160
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
IUPHAR
200
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
CAS
50-48-6
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
EVMPD
SUB05462MIG
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
CHEBI
2666
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
MERCK INDEX
m1753
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY Merck Index
NCI_THESAURUS
C62005
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
RXCUI
704
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY RxNorm
ChEMBL
CHEMBL629
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
FDA UNII
1806D8D52K
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
EPA CompTox
DTXSID7022594
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
DRUG BANK
DB00321
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
DRUG CENTRAL
180
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
DAILYMED
1806D8D52K
Created by admin on Wed Apr 02 09:57:01 GMT 2025 , Edited by admin on Wed Apr 02 09:57:01 GMT 2025
PRIMARY
ECHA (EC/EINECS)
200-041-6
Created by admin on Wed Apr 02 09:57:00 GMT 2025 , Edited by admin on Wed Apr 02 09:57:00 GMT 2025
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
Metabolizing reaction by CYP2D6: N-demethylation
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
BINDING PROTEIN->LIGAND
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
URINE
METABOLITE ACTIVE -> PARENT
MAJOR
METABOLITE -> PARENT
METABOLITE -> PARENT
URINE
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
PARENT -> IMPURITY
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
MAXIMUM TOLERATED DOSE TOXICITY DEPRESSION, INPATIENTS: 300 MG/DAY

Route of Elimination PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC