U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C20H23N.ClH
Molecular Weight 313.864
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMITRIPTYLINE HYDROCHLORIDE

SMILES

Cl.CN(C)CCC=C1C2=CC=CC=C2CCC3=CC=CC=C13

InChI

InChIKey=KFYRPLNVJVHZGT-UHFFFAOYSA-N
InChI=1S/C20H23N.ClH/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;1H

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
Molecular Formula ClH
Molecular Weight 36.461
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.

CNS Activity

Originator

Approval Year

1961
146
Targets

Targets

Primary TargetPharmacologyConditionPotency
Sodium-dependent noradrenaline transporter
39
Target ID: P23975
Gene ID: 6530.0
Gene Symbol: SLC6A2
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 3.45 nM [IC50]
Sodium-dependent serotonin transporter
41
Target ID: P31645
Gene ID: 6532.0
Gene Symbol: SLC6A4
Target Organism: Homo sapiens (Human)
Inhibitor
8504
 13.3 nM [IC50]
5-hydroxytryptamine receptor 2A
73
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Antagonist
2849
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Approved
8583
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946

inhibitor
2252
substrate
1193
substrate
1388

inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C19
2057

CYP2C8
1057

OCT1
620

OCT2
779
CYP1A2
1197

CYP2C19
1119

CYP2B6
776

UGT2B10
131

UGT1A4
399
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OCT2
782
 yes [IC50 14 uM]
OCT1
656
 yes [IC50 6.99 uM]
CYP3A4
2633
 yes [IC50 8.8 uM]
CYP2C8
1117
 yes [Inhibition 200 uM]
CYP2D6
2546
 yes [Ki 31 uM]
CYP2C19
2141
 yes [Ki 37.7 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1197
 no
CYP2C19
1119
 no
CYP2B6
776
 yes
CYP2C9
1193
 yes
CYP2D6
1388
 yes
CYP3A4
1946
 yes
UGT1A4
399
 yes
UGT2B10
131
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:2666
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2666
eMolecules
739635
https://www.emolecules.com/cgi-bin/more?vid=739635
MolPort
MolPort-001-662-651
https://www.molport.com/shop/molecule-link/MolPort-001-662-651
ZINC
ZINC000000968257
http://zinc15.docking.org/substances/ZINC000000968257
PubMed

PubMed

TitleDatePubMed
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.
2001-10
Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care.
2001-09-22
HPLC of basic drugs on microparticulate strong cation-exchange materials - a review.
2001-09-15
Efficacy of spinal manipulation for chronic headache: a systematic review.
2001-09
Drug use and five-year incidence of age-related cataracts: The Beaver Dam Eye Study.
2001-09
[Comparative studies of adverse effects in patients with refractory depression treated with amitryptyline, mianserin and unilateral ECT].
2001-08-09
Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram.
2001-08
Combined pharmacotherapy for nocturnal enuresis.
2001-08
Interaction of psychotropic drugs with monoamine oxidase in rat brain.
2001-08
Adherence to treatment regimen in depressed patients treated with amitriptyline or fluoxetine.
2001-08
Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates.
2001-08
Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.
2001-08
Efficacy of amitriptyline as a pharmacological adjunct to behavioral modification in the management of aggressive behaviors in dogs.
2001-07-14
[Ciguatera: clinical relevance of a marine neurotoxin].
2001-07-13
Cyclobenzaprine and back pain: a meta-analysis.
2001-07-09
Late-onset GM2 gangliosidosis presenting as burning dysesthesias.
2001-07
Isolated sural neuropathy presenting as lateral ankle pain.
2001-07
Antinociception by tricyclic antidepressants in the rat formalin test: differential effects on different behaviours following systemic and spinal administration.
2001-07
Mirtazepine: heir apparent to amitriptyline?
2001-06-16
The effect of amitriptyline on pain intensity and perception of stress in bruxers.
2001-06
Assessment of DNA damage in C6 glioma cells after antidepressant treatment using an alkaline comet assay.
2001-06
Acute eosinophilic pneumonia associated with amitriptyline in a hemodialysis patient.
2001-06
Retro-orbital tumour--an uncommon cause of headache in pregnancy.
2001-06
Involvement of adenosine in the effect of antidepressants on glutamate and aspartate release in the rat prefrontal cortex.
2001-06
Pharmacological modulation of SK3 channels.
2001-06
Corticotropin-releasing hormone perturbations in interstitial cystitis patients: evidence for abnormal sympathetic activity.
2001-06
Ring flexibility within tricyclic antidepressant drugs.
2001-06
High-performance liquid chromatographic method combining radiochemical and ultraviolet detection for determination of low activities of uridine 5'-diphosphate-glucuronosyltransferase.
2001-05-15
[St. John's wort: a pharmaceutical with potentially dangerous interactions].
2001-05-10
Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial.
2001-05-02
Effects of amitriptyline on diurnal variations of oxidation-reduction enzyme activities in rat lymphocytes during experimental desynchronosis.
2001-05
Antidepressant drugs in dermatology.
2001-05
Bipolar disorder after mefloquine treatment.
2001-05
Treatment of neuropathic pain with venlafaxine.
2001-05
Advances in the management of neuropathic pain.
2001-05
Inhibition of synovial plasma extravasation by preemptive administration of an antiinflammatory irrigation solution in the rat knee.
2001-05
Patterns of response to repeated total sleep deprivations in depression.
2001-05
Controlling phantom limb pain in Sierra Leone.
2001-04-21
[Sensory neuropathy in HIV infection: pathogenesis and therapy].
2001-04-14
Amitriptyline versus bupivacaine in rat sciatic nerve blockade.
2001-04
Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy.
2001-04
The effects of amitriptyline, citalopram and reboxetine on autonomic nervous system. A randomised placebo-controlled study on healthy volunteers.
2001-04
Noradrenergic dysfunction and antidepressant treatment response.
2001-04
Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective.
2001
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
Tianeptine: a review of its use in depressive disorders.
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
[Cardiac arrest following amitriptylin and adrenaline].
1975-06-16
Patents

Patents

JP2007512339A
43
JP2007525670A
150
JP2011528275A
456
JP4653399B2
50
JPS5569567A
7

Sample Use Guides

In Vivo Use Guide
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 Mon Mar 31 18:04:15 GMT 2025
Edited
by admin
on Mon Mar 31 18:04:15 GMT 2025
Record UNII
26LUD4JO9K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
AMITRIPTYLINE HYDROCHLORIDE
EP   HSDB   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
ETRAFON-A COMPONENT AMITRIPTYLINE HYDROCHLORIDE
Preferred Name English
AMITRIPTYLINE HYDROCHLORIDE [MI]
Common Name English
LIMBITROL DS COMPONENT AMITRIPTYLINE HYDROCHLORIDE
Common Name English
LIMBITROL COMPONENT AMITRIPTYLINE HYDROCHLORIDE
Common Name English
NSC-104210
Code English
AMITRIPTYLINE HYDROCHLORIDE [MART.]
Common Name English
AMITRIPTYLINI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
SYNEUDON
Common Name English
Amitriptyline hydrochloride [WHO-DD]
Common Name English
ENDEP
Brand Name English
AMITID
Brand Name English
AMITRIPTYLINE HYDROCHLORIDE [WHO-IP]
Common Name English
NOVOPROTECT
Common Name English
ELAVIL
Brand Name English
ETRAVIL
Brand Name English
AMITRIPTYLINE HYDROCHLORIDE [USP IMPURITY]
Common Name English
AMITRIL
Brand Name English
AMITRIPTYLINE HYDROCHLORIDE [EP IMPURITY]
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [VANDF]
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
NIH 10794
Code English
AMITRIPTYLINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
AMITRIPTYLINE HCL
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [JAN]
Common Name English
AMITRIPTYLINE HYDROCHLORIDE [USP-RS]
Common Name English
1-PROPANAMINE, 3-(10,11-DIHYDRO-5H-DIBENZO(A,D)CYCLOHEPTEN-5-YLIDENE)-N,N-DIMETHYL-, HYDROCHLORIDE
Systematic Name English
AMITRIPTYLINE HYDROCHLORIDE [HSDB]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C94727
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
Code System Code Type Description
RS_ITEM_NUM
1029002
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
CAS
549-18-8
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
DAILYMED
26LUD4JO9K
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
AMITRIPTYLINE HYDROCHLORIDE
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY Description: Colourless crystals or a white or almost white powder; odourless or almost odourless. Solubility: Soluble in 1 part of water and in 1.5 parts of ethanol (~750 g/l) TS; practically insoluble in ether R. Category: Antidepressant. Storage: Amitriptyline hydrochloride should be kept in a tightly closed container, protected from light. Additional information: Amitriptyline hydrochloride has a bitter and burning taste that is followed by a sensation of numbness. Even in the absence of light, Amitriptyline hydrochloride is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. Definition: Amitriptyline hydrochloride contains not less than 99.0% and not more than 101.5% of C20H23N,HCl, calculated with reference to the dried substance.
SMS_ID
100000090311
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
ECHA (EC/EINECS)
208-964-6
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
PUBCHEM
11065
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
FDA UNII
26LUD4JO9K
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
DRUG BANK
DBSALT000009
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
MERCK INDEX
m1753
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY Merck Index
NSC
104210
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
ChEMBL
CHEMBL629
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
EVMPD
SUB00474MIG
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
NCI_THESAURUS
C28819
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
RXCUI
203168
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY RxNorm
EPA CompTox
DTXSID9033187
Created by admin on Mon Mar 31 18:04:15 GMT 2025 , Edited by admin on Mon Mar 31 18:04:15 GMT 2025
PRIMARY
Related Record Type Details
Structure of AMITRIPTYLINE HYDROCHLORIDE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
Structure of Amitriptyline
PARENT -> SALT/SOLVATE
Structure of AMITRIPTYLINE HYDROCHLORIDE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
Related Record Type Details
Structure of NORTRIPTYLINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of Dibenzosuberol
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of CYCLOBENZAPRINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of NORTRIPTYLINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of Dibenzosuberone
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of Amitriptynol
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Structure of N-nitroso-desmethyl-amitriptyline
IMPURITY -> PARENT
Structure of Dibenzosuberone
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of Amitriptynol
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Structure of CYCLOBENZAPRINE
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of Amitriptyline
ACTIVE MOIETY
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966