D0006 | Amitriptyline

Molecular Formula C20H23N
Molecular Weight 277.4
State solid
Clearance The mean systemic clearance (Cls) is 39.24 ± 10.18 L/h (range: 24.53-53.73 L/h) [FDA Label]. No clear effect of older age on the pharmacokinetics of amitriptyline has been determined, although it is possible that clearance may be decreased [A174661].
Volume of distribution The apparent volume of distribution (Vd)beta estimated after intravenous administration is 1221 L±280 L; range 769-1702 L (16±3 L/kg) [FDA Label]. It is found widely distributed throughout the body [A174661]. Amitriptyline and the main metabolite _nortriptyline_ pass across the placental barrier and small amounts are present in breast milk [FDA Label].
Route of elimination Amitriptyline and its metabolites are mainly excreted in the urine. Virtually the entire dose is excreted as glucuronide or sulfate conjugate of metabolites, with approximately 2% of unchanged drug appearing in the urine [FDA Label]. 25-50% of a single orally administered dose is excreted in urine as inactive metabolites within 24 hours [FDA label]. Small amounts are excreted in feces via biliary elimination [F3454].
Protein binding Very highly protein bound (95%) in plasma and tissues [FDA Label].
Half life The elimination half-life (t1⁄2 beta) amitriptyline after peroral administration is about 25 hours (24.65 ± 6.31 hours; range 16.49-40.36 hours) [FDA Label].
Absorption Rapidly absorbed following oral administration (bioavailability is 30-60% due to first pass metabolism). Peak plasma concentrations are reached 2-12 hours after oral or intramuscular administration [FDA label]. Steady-state plasma concentrations vary greatly and this variation may be due to genetic differences [F3454].
Trade names Elavil
Description tricyclic antidepressant (TCA) with analgesic properties


N06CA01 Amitriptyline and psycholeptics

[N06CA] Antidepressants in combination with psycholeptics



[N] Nervous system

N06AA09 Amitriptyline

[N06AA] Non-selective monoamine reuptake inhibitors



[N] Nervous system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
UNCOUPLING rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay Negative 53
ELECTRON TRANSPORT CHAIN pig brain mitochondria decrease 60
ELECTRON TRANSPORT CHAIN rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay Negative 53
GLUCOSE GALACTOSE IC50 RATIO 70.9 ± 16.8, 72.0 ± 5.3, 1, 68.1 ± 9.1, 67.0 ± 11.6, 1 4hr H9c2 cells high-glucose–galactose cell viability assay with JC-1 mitochondrial membrane potential and ATP-depletion assays (CellTiter-Glo reagent ). glucose/galactose IC50 ratio (JC-1 IC50 in glucose, JC-1 IC50 in galactose, JC-1 glu/gla, ATP IC50 in glucose, ATP IC50 in galactose, ATP glu/gla ) 50

Pictogram Signal Statements Precautionary Statement Codes

Aggregated GHS information provided by 196 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H301+H311+H331 (80.1%): Toxic if swallowed, in contact with skin or if inhaled [Danger Acute toxicity, oral

acute toxicity, dermal

acute toxicity, inhalation]

H302 (19.39%): Harmful if swallowed [Warning Acute toxicity, oral]

H318 (80.1%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H361 (80.1%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H410 (80.1%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

P201, P202, P261, P264, P270, P271, P273, P280, P281, P301+P310, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P311, P312, P321, P322, P330, P361, P363, P391, P403+P233, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

H301: Toxic if swallowed [Danger Acute toxicity, oral]

H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

P201, P202, P264, P270, P281, P301+P310, P308+P313, P321, P330, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
dog LD50 intramuscular > 23mg/kg (23mg/kg) Oyo Yakuri. Pharmacometrics. Vol. 6, Pg. 899, 1972.
women TDLo oral 10mg/kg (10mg/kg) behavioral: "hallucinations, distorted perceptions" Canadian Medical Association Journal. Vol. 129, Pg. 1203, 1983.
child TDLo oral 58mg/kg (58mg/kg) Southern Medical Journal. Vol. 82, Pg. 1588, 1989.
monkey LDLo intravenous 20300ug/kg (20.3mg/kg) Indian Journal of Experimental Biology. Vol. 22, Pg. 539, 1984.
women TDLo oral 84mg/kg (84mg/kg) cardiac: ekg changes not diagnostic of above Japanese Journal of Toxicology. Vol. 5, Pg. 69, 1992.
man TDLo oral 1564mg/kg/2Y- (1564mg/kg) Italian Journal of Neurological Sciences. Vol. 9, Pg. 89, 1988.
guinea pig LDLo intravenous 35mg/kg (35mg/kg) Drugs of the Future. Vol. 8, Pg. 949, 1983.
man LDLo oral 29mg/kg (29mg/kg) Human & Experimental Toxicology. Vol. 9, Pg. 257, 1990.
man TDLo oral 714ug/kg/1D-I (0.714mg/kg) Human Psychopharmacology. Vol. 7, Pg. 273, 1992.
guinea pig LDLo intravenous 52mg/kg (52mg/kg) cardiac: other changes Therapie. Vol. 20, Pg. 67, 1965.
women TDLo intramuscular 240ug/kg/36H- (0.24mg/kg) behavioral: convulsions or effect on seizure threshold Lancet. Vol. 1, Pg. 390, 1968.
rat LD50 oral 240mg/kg (240mg/kg) Oyo Yakuri. Pharmacometrics. Vol. 6, Pg. 889, 1972.
child LDLo oral 62500ug/kg (62.5mg/kg) New England Journal of Medicine. Vol. 267, Pg. 1031, 1962.
mouse LD50 intravenous 16mg/kg (16mg/kg) behavioral: changes in motor activity (specific assay) Journal of Medicinal Chemistry. Vol. 17, Pg. 65, 1974.
dog LDLo oral 200mg/kg (200mg/kg) Oyo Yakuri. Pharmacometrics. Vol. 6, Pg. 889, 1972.
cat LD50 oral 37mg/kg (37mg/kg) Drug Development Research. Vol. 22, Pg. 385, 1991.
women LDLo oral 19mg/kg (19mg/kg) Lancet. Vol. 2, Pg. 543, 1963.
mouse LD50 intravenous 21mg/kg (21mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 21, Pg. 808, 1971.
rat LD50 intraperitoneal 67mg/kg (67mg/kg) Drugs in Japan Vol. -, Pg. 49, 1990.
human TDLo oral 2mg/kg/3D-I (2mg/kg) British Journal of Clinical Pharmacology. Vol. 49, Pg. 118, 2000.
man TDLo oral 14286ug/kg (14.286mg/kg) Lancet. Vol. 2, Pg. 543, 1963.
human TDLo oral 200mg/kg (200mg/kg) JAMA, Journal of the American Medical Association. Vol. 230, Pg. 1405, 1974.
man TDLo unreported 45mg/kg/21D (45mg/kg) Lancet. Vol. 2, Pg. 1202, 1972.
man TDLo oral 60mg/kg/3W-I (60mg/kg) Journal of Clinical Psychiatry. Vol. 53, Pg. 160, 1992.
mouse LD50 oral 99mg/kg (99mg/kg) Doklady Akademii Nauk SSSR. Proceedings of the Academy of Sciences of the USSR. For English translation, see DBIOAM and DKBSAS. Vol. 335, Pg. 388, 1994.
dog LDLo subcutaneous 50mg/kg (50mg/kg) Pharmacologist. Vol. 11, Pg. 283, 1969.
child LDLo oral 62500ug/kg (62.5mg/kg) American Journal of Diseases of Children. Vol. 106, Pg. 501, 1963.
rat LD50 intravenous 14mg/kg (14mg/kg) "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972Vol. -, Pg. 61, 1972.
mouse LD50 subcutaneous 100mg/kg (100mg/kg) United States Patent Document. Vol. #4605673,
women TDLo oral 60mg/kg (60mg/kg) Journal of Toxicology, Clinical Toxicology. Vol. 19, Pg. 67, 1982.
mouse LD50 subcutaneous 80mg/kg (80mg/kg) Oyo Yakuri. Pharmacometrics. Vol. 6, Pg. 889, 1972.
women TDLo oral 18500ug/kg (18.5mg/kg) Gekkan Yakuji. Pharmaceuticals Monthly. Vol. 35, Pg. 795, 1993.
rabbit LD50 intraperitoneal 58700ug/kg (58.7mg/kg) lungs, thorax, or respiration: cyanosis Journal of Toxicology, Clinical Toxicology. Vol. 19, Pg. 321, 1982.
child TDLo oral 4500ug/kg (4.5mg/kg) behavioral: sleep British Medical Journal. Vol. 3, Pg. 663, 1967.
mouse LD50 intraperitoneal 48400ug/kg (48.4mg/kg) Farmakologiya i Toksikologiya Vol. 53(4), Pg. 19, 1990.
rabbit LD50 intravenous 8600ug/kg (8.6mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 15, Pg. 863, 1965.
mouse LD50 intraperitoneal 65mg/kg (65mg/kg) Journal of Drug Research. Vol. 16, Pg. 7, 1985.
mouse LD50 oral 140mg/kg (140mg/kg) Wiener Medizinische Wochenschrift. Vol. 111, Pg. 256, 1961.
dog LD50 intravenous > 27mg/kg (27mg/kg) Oyo Yakuri. Pharmacometrics. Vol. 6, Pg. 899, 1972.
child TDLo oral 4167ug/kg (4.167mg/kg) New England Journal of Medicine. Vol. 267, Pg. 1031, 1962.
infant TDLo oral 50mg/kg (50mg/kg) American Journal of Diseases of Children. Vol. 130, Pg. 507, 1976.
rat LD50 subcutaneous 385mg/kg (385mg/kg) European Journal of Pharmacology. Vol. 32, Pg. 108, 1975.
rabbit LD50 intravenous 9900ug/kg (9.9mg/kg) "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972Vol. -, Pg. 61, 1972.
mouse LD50 unreported 80mg/kg (80mg/kg) autonomic nervous system: "smooth muscle relaxant (mechanism undefined, spasmolytic)" Journal of Medicinal Chemistry. Vol. 10, Pg. 418, 1967.
women TDLo oral 16800ug/kg/2W (16.8mg/kg) Lancet. Vol. 1, Pg. 426, 1968.
rat LD50 oral 320mg/kg (320mg/kg) Arzneimittel-Forschung. Drug Research. Vol. 15, Pg. 863, 1965.
human TDLo oral 14mg/kg (14mg/kg) cardiac: other changes Proceedings of the European Society for the Study of Drug Toxicity. Vol. 6, Pg. 171, 1965.
rat LD50 intraperitoneal 72mg/kg (72mg/kg) Polish Journal of Pharmacology and Pharmacy. Vol. 27, Pg. 503, 1975.
women TDLo oral 13500ug/kg/3D (13.5mg/kg) Lancet. Vol. 1, Pg. 390, 1968.

  • Depressive symptom

  • (3-(5,6-dihydrodibenzo[b,f][7]annulen-11-ylidene)propyl)dimethylamine 1-Propanamine, 3-(10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl- 1-Propanamine, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-
    10,11-Dihydro-5-(.gamma.-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene 10,11-Dihydro-5-(gamma-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene 10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-.DELTA.5,.gamma.-propylamine
    10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-delta(5),gamma-propylamine 10,11-Dihydro-N,N-dimethyl-5H-dibenzo(a,d)heptalene-delta(sup 5),gamma-propylamine 10,11-dihydro-5-(gamma-dimethylaminopropylidene)-5H-dibenzo[a,d]cycloheptene
    10,11-dihydro-N,N-dimethl-5H-dibenzo[a,d]cycloheptene-(delta(5, gamma))-propylamine 1409-EP2269989A1 1409-EP2275420A1
    1409-EP2277861A1 1409-EP2298313A1 1409-EP2298731A1
    1409-EP2298764A1 1409-EP2298765A1 1409-EP2305652A2
    1409-EP2305669A1 1409-EP2314585A1 1806D8D52K
    3-(10,11-Dihydro-5H-dibenzo(a,d)cyclohepten-5-yliden)-N,N-dimethylpropylamin 3-(10,11-Dihydro-5H-dibenzo(a,d)cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine 3-(10,11-Dihydro-5H-dibenzo-[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine, hydrochloride
    3-(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethyl-1-propanamine 3-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine 3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)-N,N-dimethylpropan-1-amine
    3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethylpropan-1-amine 3-(5,6-dihydrodibenzo[[?],[?]][7]annulen-11-ylidene)-N,N-dimethyl-propan-1-amine 412A072
    5-(.gamma.-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene 5-(.gamma.-Dimethylaminopropylidene)-5H-Dibenzo[a,d][1,4]cycloheptadiene 5-(.gamma.-Dimethylaminopropylidene)-5H-dibenzo(a,d)-10,11-dihydrocycloheptene
    5-(.gamma.-Dimethylaminopropylidine)-5H-dibenzo(a,d)(1,4)cycloheptadiene 5-(3'-Dimethylaminopropylidene)-dibenzo-(a,d)(1,4)-cycloheptadiene 5-(3'-Dimethylaminopropylidene)-dibenzo-[a,d][1,4]-cycloheptadiene
    5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptatriene 5-(3-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene 5-(3-Dimethylaminopropylidene)-5H-dibenzo[a,d]-10,11-dihydrocycloheptene
    5-(3-dimethylaminopropylidene)dibenzo[a,d][1,4]-cycloheptadiene 5-(gamma-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo(a,d)cycloheptene 5-(gamma-Dimethylaminopropylidene)-5H-Dibenzo[a,d][1,4]cycloheptadiene
    5-(gamma-Dimethylaminopropylidene)-5H-dibenzo(a,d)(1,4)cycloheptadiene 5-(gamma-Dimethylaminopropylidene)-5H-dibenzo[a,d]10,11-dihydrocycloheptene 5-(gamma-Dimethylaminopropylidine)-5H-dibenzo(a,d)(1,4)cycloheptadiene
    50-48-6 5H-Dibenzo(a,d)cycloheptene-.delta.(sup 5),.gamma.-propylamine, 10,11-dihydro-N,N-dimethyl- 5H-Dibenzo(a,d)cycloheptene-delta(sup 5),gamma-propylamine, 10,11-dihydro-N,N-dimethyl-
    5H-Dibenzo(a,d)cycloheptene-delta5,gamma-propylamine, 10,11-dihydro-N,N-dimethyl- 5H-Dibenzo[a,d]cycloheptene-.delta.5,.gamma.-propylamine, 10,11-dihydro-N,N-dimethyl- 5H-Dibenzo[a,d]cycloheptene-Delta5,gamma-propylamine, 10,11-dihydro-N,N-dimethyl- (6CI,8CI) 5-(gamma-Dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene
    AB00053417-12 AB00053417_13 AB00053417_14
    AB00514631 AKOS000512694 API0001457
    ARONIS24381 Adepress Adepril
    Amitril Amitriprolidine Amitriptilina
    Amitriptilina [INN-Spanish] Amitriptilina [Italian] Amitriptylin
    Amitriptylin [German] Amitriptyline (INN) Amitriptyline [INN:BAN]
    Amitriptylinum Amitriptylinum [INN-Latin] Amitryptiline
    Amitryptyline Amytriptiline Amytriptylin
    BBC/541 BBL028529 BCP09083
    BDBM50020712 BIDD:GT0115 BPBio1_000317
    BRD-K53737926-003-05-4 BRD-K53737926-003-14-6 BRN 2217885
    BSPBio_000287 BSPBio_001836 C06824
    CAS-549-18-8 CCG-204207 CCRIS 9174
    CHEBI:2666 CHEMBL629 D07448
    DB00321 DTXSID7022594 Damilan
    Damilen Damitriptyline DivK1c_000766
    Domical (Salt/Mix) EC 200-041-6 EINECS 200-041-6
    Elanil Elavil FT-0653242
    Flavyl GTPL200 HSDB 3007
    IDI1_000766 KBio1_000766 KBio2_000424
    KBio2_002261 KBio2_002992 KBio2_004829
    KBio2_005560 KBio2_007397 KBio3_001336
    KBio3_002741 KBioGR_000592 KBioGR_002261
    L001041 LS-60747 Lantron
    Laroxil Laroxyl (Salt/Mix) Laroxyl (TN)
    Lentizol (Salt/Mix) Limbitrol Lopac-A-8404
    Lopac0_000112 MCULE-3537115467 MK 230
    MRF-0000533 N 750 NCGC00015095-01
    NCGC00015095-02 NCGC00015095-03 NCGC00015095-04
    NCGC00015095-05 NCGC00015095-06 NCGC00015095-07
    NCGC00015095-08 NCGC00015095-09 NCGC00015095-10
    NCGC00015095-11 NCGC00015095-12 NCGC00024433-04
    NCGC00183047-01 NINDS_000766 NSC169910
    Oprea1_479304 PDSP1_001564 PDSP2_001548
    Prestwick0_000074 Prestwick1_000074 Prestwick2_000074
    Prestwick3_000074 Proheptadiene Q58397
    Redomex Ro 4-1575 SBB080793
    SBI-0050100.P004 SCHEMBL7824 SPBio_000082
    SPBio_002208 STK525215 Sarotex
    Seroten Spectrum2_000101 Spectrum3_000298
    Spectrum4_000146 Spectrum5_000806 Spectrum_000044
    Triptanol Triptilin Triptisol
    Triptizol (Salt/Mix) Tryptanol UNII-1806D8D52K
    Vanatrip (Salt/Mix) W-109252 ZINC968257
    ZX-AS004743 amitriptyline cMAP_000001
    dimethyl({3-[(2E)-tricyclo[^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene]propyl})amine dimethyl({3-[(2Z)-tricyclo[^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene]propyl})amine

    DrugBank Name Amitriptyline
    DrugBank DB00321
    CAS Number 30227-34-0, 50-48-6, 549-18-8
    PubChem Compound 2160
    KEGG Compound ID C06824
    KEGG Drug D07448
    PubChem.Substance 46508798
    ChEBI 2666
    PharmGKB PA448385
    ChemSpider 2075
    BindingDB 50020712.0
    TTD DNC001466
    Wikipedia Amitriptyline
    HET TP0
    DPD 10187|9881|5979

    1. Vuda et al. (2016)