ContaminantDB: Amitriptyline

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (44)XML

Record Information

Version

1.0

Creation Date

2009-07-03 22:04:59 UTC

Update Date

2026-03-25 19:14:27 UTC

Accession Number

CHEM002063

Identification

Common Name

Amitriptyline

Class

Small Molecule

Description

Amitriptyline hydrochloride is a dibenzocycloheptene-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, amitriptyline does not affect mood or arousal, but may cause sedation. In depressed individuals, amitriptyline exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H₁ receptors, α₁-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Amitriptyline may be used to treat depression, chronic pain (unlabeled use), irritable bowel syndrome (unlabeled use), diabetic neuropathy (unlabeled use), post-traumatic stress disorder (unlabeled use), and for migraine prophylaxis (unlabeled use).

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
Suspected Compounds
T3DB toxins

Contaminant Type

Adrenergic Uptake Inhibitor
Amine
Analgesic, Non-Narcotic
Antidepressive Agent, Tricyclic
Drug
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
10,11-Dihydro-5-(gamma-dimethylaminopropylidene)-5H-dibenzo(a,D)cycloheptene	ChEBI
10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,D)heptalene-Delta(5),gamma-propylamine	ChEBI
3-(10,11-Dihydro-5H-dibenzo(a,D)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine	ChEBI
3-(10,11-Dihydro-5H-dibenzo[a,D]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine	ChEBI
5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,D)cycloheptatriene	ChEBI
5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,D)cycloheptene	ChEBI
5-(gamma-Dimethylaminopropylidene)-5H-dibenzo[a,D][1,4]cycloheptadiene	ChEBI
Amitriptylin	ChEBI
Laroxyl	Kegg
10,11-Dihydro-5-(g-dimethylaminopropylidene)-5H-dibenzo(a,D)cycloheptene	Generator
10,11-Dihydro-5-(γ-dimethylaminopropylidene)-5H-dibenzo(a,D)cycloheptene	Generator
10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,D)heptalene-delta(5),g-propylamine	Generator
10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,D)heptalene-δ(5),γ-propylamine	Generator
5-(g-Dimethylaminopropylidene)-5H-dibenzo[a,D][1,4]cycloheptadiene	Generator
5-(Γ-dimethylaminopropylidene)-5H-dibenzo[a,D][1,4]cycloheptadiene	Generator
10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,D)heptalene-δ(5),g-propylamine	HMDB
Amitriprolidine	HMDB
Amitryptiline	HMDB
Amitryptyline	HMDB
Amytriptiline	HMDB
APS brand OF amitriptyline hydrochloride	HMDB
Amitriptylin beta	HMDB
Apo-amitriptyline	HMDB
Apotex brand OF amitriptyline hydrochloride	HMDB
Bayer brand OF amitriptyline hydrochloride	HMDB
Desitin, amitriptylin	HMDB
Domical	HMDB
Douglas brand OF amitriptyline hydrochloride	HMDB
Goldshield brand OF amitriptyline hydrochloride	HMDB
Merck brand OF amitriptyline hydrochloride	HMDB
Merck sharp and dohme brand OF amitriptyline embonate	HMDB
Rodleben brand OF amitriptyline hydrochloride	HMDB
Saroten	HMDB
Tryptine	HMDB
Amitriptylin RPH	HMDB
Amitrol	HMDB
Apo amitriptyline	HMDB
ApoAmitriptyline	HMDB
Cahill may roberts brand OF amitriptyline hydrochloride	HMDB
Novoprotect	HMDB
Rhône poulenc rorer brand OF amitriptyline hydrochloride	HMDB
Tryptanol	HMDB
Tryptizol	HMDB
beta, Amitriptylin	HMDB
Alphapharm brand OF amitriptyline hydrochloride	HMDB
Amitrip	HMDB
Amitriptylin-neuraxpharm	HMDB
Amitriptylinneuraxpharm	HMDB
Anapsique	HMDB
Cahill may roberts brand OF amitriptyline embonate	HMDB
Damilen	HMDB
Desitin brand OF amitriptyline hydrochloride	HMDB
Endep	HMDB
Hexal brand OF amitriptyline hydrochloride	HMDB
Krewel brand OF amitriptyline hydrochloride	HMDB
Protea brand OF amitriptyline hydrochloride	HMDB
Psicofarma brand OF amitriptyline hydrochloride	HMDB
RPH, Amitriptylin	HMDB
Rhône-poulenc rorer brand OF amitriptyline hydrochloride	HMDB
Roche brand OF amitriptyline hydrochloride	HMDB
Sarotex	HMDB
Syneudon	HMDB
Triptafen	HMDB
Amineurin	HMDB
Amitriptylin desitin	HMDB
Amitriptylin neuraxpharm	HMDB
Amitriptyline hydrochloride	HMDB
Amrad brand OF amitriptyline hydrochloride	HMDB
Betapharm brand OF amitriptyline hydrochloride	HMDB
DDSA brand OF amitriptyline hydrochloride	HMDB
Elavil	HMDB
Lentizol	HMDB
Lundbeck brand OF amitriptyline hydrochloride	HMDB
Merck sharp and dohme brand OF amitriptyline hydrochloride	HMDB
Neuro hexal brand OF amitriptyline hydrochloride	HMDB
Parke davis brand OF amitriptyline hydrochloride	HMDB
Zeneca brand OF amitriptyline hydrochloride	HMDB
Neuraxpharm brand OF amitriptyline hydrochloride	HMDB

Chemical Formula

C₂₀H₂₃N

Average Molecular Mass

277.403 g/mol

Monoisotopic Mass

277.183 g/mol

CAS Registry Number

50-48-6

IUPAC Name

dimethyl(3-{tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine

Traditional Name

amitriptyline

SMILES

CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12

InChI Identifier

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

InChI Key

KRMDCWKBEZIMAB-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as dibenzocycloheptenes. Dibenzocycloheptenes are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Dibenzocycloheptenes

Sub Class

Not Available

Direct Parent

Dibenzocycloheptenes

Alternative Parents

Substituents

Dibenzocycloheptene
Tertiary aliphatic amine
Tertiary amine
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Organonitrogen compound
Amine
Aromatic homopolycyclic compound

Molecular Framework

Aromatic homopolycyclic compounds

External Descriptors

tertiary amine (CHEBI:2666 )
organic tricyclic compound (CHEBI:2666 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

adrenergic uptake inhibitor

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White, odorless, crystalline compound (4).

Experimental Properties

Property	Value
Melting Point	187-189.5°C
Boiling Point	Not Available
Solubility	9.71 mg/L (at 24°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.0045 g/L	ALOGPS
logP	5.1	ALOGPS
logP	4.81	ChemAxon
logS	-4.8	ALOGPS
pKa (Strongest Basic)	9.76	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	1	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	3.24 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	101.51 m³·mol⁻¹	ChemAxon
Polarizability	33.74 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4i-9010000000-2afae55587735e5a8ce1	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4i-9010000000-2afae55587735e5a8ce1	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-9040000000-fe5eb711e5e29e99efed	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-05po-5890000000-4cce07a2d07337e4ce90	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-001i-1590000000-35080e23f36a6ed30005	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0090000000-66d4e2dc0e65719c8949	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0190000000-18fad36e219aa0091dcf	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-05o3-3980000000-bd3bb65e31837e45268f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0aou-2940000000-c3c71a4ddeb15eb427b4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-05mo-2930000000-f6bc4a5899aed7b3047e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0fr6-2930000000-c348567e54820b6ddff3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0090000000-fae7f4e9cc1f20e9a2dd	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-004i-0190000000-42ecf4fcfbd4bd102322	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-05o3-3980000000-69e1e5d2fdd46de25ba4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0aou-2940000000-853a0f18213b600d48ae	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-05mo-2930000000-9493535ee63a9a708527	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0fr6-2930000000-fba97ca65c4bf1940385	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-001i-1690000000-99ea606fc86c8400c4ce	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004i-0090000000-8155764b5e04e44b4ca2	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004i-0190000000-7e3a5d063f540759d63f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0apl-0960000000-e35715828f4c02816f19	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0lfu-0940000000-a6befd2c2f6b01d0c348	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0190000000-e92473ae05e0e7ecb6ed	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-003r-3390000000-db46c53d9e4e8729d7f3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-5940000000-1c8f604ddf2e5e56560e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-004i-0090000000-90c019b2f9a1e35d9e6d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-004i-1090000000-a8d8a7f9b985c30547f2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0536-7290000000-3505755fe83fe73e694f	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0a4i-9210000000-989cd234a8cdf04c5f69	Spectrum

Toxicity Profile

Route of Exposure

Oral (1) Rapidly and well absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations occur 2-12 hours following oral or intramuscular administration.

Mechanism of Toxicity

Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.

Metabolism

Amitriptyline is rapidly and well absorbed following oral administration. Exclusively hepatic, with first pass effect. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline. Route of Elimination: Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with little unchanged drug appearing in the urine. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours. Small amounts are excreted in feces via biliary elimination. Half Life: 10 to 50 hours, with an average of 15 hours

Toxicity Values

LD50: 350 mg/kg (Oral, Mouse) (1)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of depression, chronic pain, irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation and insomnia, and migraine prophylaxis.

Minimum Risk Level

Not Available

Health Effects

Some rare side effects include tinnitus, hypotension, mania, psychosis, heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, and hepatic toxicity.Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold (1, 4).

Symptoms

Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.

Treatment

Consider gastric lavage only if within one hour of a potentially fatal overdose. Give 50 grams of charcoal if within one hour of ingestion. Prolonged resuscitation may be successful in case of cardiac arrest. Give sodium bicarbonate in case of arrhythmias. (2)

Concentrations

Not Available

External Links

DrugBank ID

DB00321

HMDB ID

HMDB0014466

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

C00022968

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Manfred Durr, Benedikt Gajdos, Klaus-Dieter Gneuss, Ekkehard Harhausen, Jurgen Seidel, “Pharmaceutical amitriptylin oxide preparation and process for its manufacture.” U.S. Patent US4567202, issued January 28, 1986.

MSDS

Link

General References

1. https://www.ncbi.nlm.nih.gov/pubmed/?term=15554244

2. https://www.ncbi.nlm.nih.gov/pubmed/?term=18359012

3. https://www.ncbi.nlm.nih.gov/pubmed/?term=24447704

4. Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6.

Amitriptyline (CHEM002063)

Structure for CHEM002063: Amitriptyline