Amitriptyline

Amitriptyline	Last updated: 09/09/2025
(Not known by any other names)

GENERAL INFORMATION

Description

Amitriptyline is a tricyclic antidepressant

Examples of veterinary uses

Used to treat many behavioral disorders in pets such as excessive grooming and urine spraying

Examples of species treated

Cats; Dogs

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Amitriptyline exhibits geometrical (E/Z) isomerism and conformational isomerism. The molecule contains a tertiary amine and a double bond in its side chain, which allows for E (trans) and Z (cis) configurations depending on the spatial arrangement around the double bond. In addition, while amitriptyline itself does not have chiral centres, its metabolites, such as nortriptyline, do exhibit stereoisomerism, including R and S enantiomers, which can differ in therapeutic effect and metabolism.

Chemical formula

C₂₀H₂₃N

Canonical SMILES

CN(C)CCC=C1C2=CC=CC=C2CCC3=CC=CC=C31

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

KRMDCWKBEZIMAB-UHFFFAOYSA-N

International Chemical Identifier (InChI)

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

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
amitriptyline hydrochloride	Variant

General status

Veterinary substance type

Medicinal drug: Tricyclic antidepressant

Substance groups

Unclassified substance

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Acts via the inhibition of serotonin and other transmitters at presynaptic nerve terminals.

Molecular targets

[Sodium-dependent noradrenaline transporter, Inhibitor], [Sodium-dependent serotonin transporter, Inhibitor], [ 5-hydroxytryptamine receptor 2A, Antagonist], [5-hydroxytryptamine receptor 1A, Inhibitor]

CAS RN

50-48-6

EC number

200-041-6

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Antidepressants in combination with psycholeptics: Amitriptyline and psycholeptics

ATCvet Code

QN06CA01

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

277.40

PIN (Preferred Identification Name)

3-(10,11-dihydro-5H-dibenzo(a,d)cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine

IUPAC name

3-(10,11-dihydro-5H-dibenzo(a,d)cycloheptene-5-ylidene)-N,N-dimethylpropan-1-amine

CAS name

10,11-dihydro-5-(g-dimethylaminopropylidene)-5H-dibenzo(a,d)cycloheptene

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

White powdery solid

Related substances & organisms

amitriptyline hydrochloride

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1960, discovered

Example manufacturers & suppliers of products using this active now or historically

Zeneca

Example products using this active

Elavil

Formulation and application details

Typically supplied as oral tablets and liquid suspensions for oral administration

Commercial production

The production of amitriptyline typically begins with the synthesis of its tricyclic core, starting from dibenzosuberone, a key intermediate. This compound undergoes alkylation with 3-dimethylaminopropyl chloride in the presence of a base such as potassium carbonate, forming the side chain that includes the dimethylamino group. The reaction is usually carried out in an organic solvent like acetone or ethanol under reflux conditions. The resulting crude product is then purified to isolate amitriptyline free base, which is subsequently converted into amitriptyline hydrochloride, the pharmaceutically active salt form.

Impact on climate of production and use

Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

Solubility - In water at 20 °C (mg l⁻¹)

9.71

Low

Solubility - In organic solvents at 20 °C (mg l⁻¹)

Melting point (°C)

196

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

Octanol-water partition coefficient at pH 7, 20 °C

Log P

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

9.4

Vapour pressure at 20 °C (mPa)

Henry's law constant at 25 °C (Pa m³ mol⁻¹)

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

Maximum UV-vis absorption L mol⁻¹ cm⁻¹

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Amitriptyline has been found in treated wastewater, surface water and sludge indicating loss via animal waste.

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7

Value

Note

Water-sediment DT₅₀ (days)

Water phase only DT₅₀ (days)

Sediment phase only DT₅₀ (days)

Air degradation

As this parameter is not normally measured directly, a surrogate measure is used: ‘Photochemical oxidative DT₅₀’. Where data is available, this can be found in the Fate Indices section below.

Decay in stored produce DT₅₀

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d (mL g⁻¹)

K_oc (mL g⁻¹)

Notes and range

Freundlich

K_f (mL g⁻¹)

K_foc (mL g⁻¹)

¹/_n

Notes and range

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

Bio-concentration factor

BCF (l kg⁻¹)

CT₅₀ (days)

Known metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

320

Rat

Moderate

Mammals - Short term dietary NOEL

(mg kg⁻¹)

(ppm diet)

Mammals - Chronic 21d NOAEL (mg kg⁻¹ bw d⁻¹)

Birds - Acute LD₅₀ (mg kg⁻¹)

Birds - Short term dietary (LC₅₀/LD₅₀)

Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)

Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹ dw soil)

Earthworms - Chronic NOEC, reproduction (mg kg⁻¹ dw soil)

Soil micro-organisms

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

Non-target plants

Vegetative vigour ER₅₀ (g ha⁻¹)

Seedling emergence ER₅₀ (g ha⁻¹)

Honeybees (Apis spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Unknown mode acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Chronic

Notes

Bumblebees (Bombus spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Mason bees (Osmia spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Other bee species (1)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Other bee species (2)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Beneficial insects (Ladybirds)

Beneficial insects (Lacewings)

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites)

Beneficial insects (Ground beetles)

Aquatic ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Temperate Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

Temperate Freshwater Fish - Chronic 21 day NOEC (mg l⁻¹)

Tropical Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

Temperate Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

0.004

Daphnia magna as mM

High

Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)

Tropical Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

Aquatic crustaceans - Acute 96 hour LC₅₀ (mg l⁻¹)

Sediment dwelling organisms - Acute 96 hour LC₅₀ (mg l⁻¹)

Sediment dwelling organisms - Chronic 28 day NOEC, static, water (mg l⁻¹)

Sediment dwelling organisms - Chronic 28 day NOEC, sediment (mg kg⁻¹)

Aquatic Plants (free-floating, fonds growth, fresh) - 7 day (mg l⁻¹)

Aquatic plants (rooted, growth rate, fresh) - 14 day (mg l⁻¹)

Algae - Acute (growth rate, fresh; mg l⁻¹)

Algae - Chronic (growth rate, fresh; mg l⁻¹)

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves

HUMAN HEALTH AND PROTECTION

General

Property

Value

Source; quality score; and other information

Interpretation

Threshold of Toxicological Concern (Cramer Class)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

320

Rat

Moderate

Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 72 mg kg⁻¹

Rat

Intravenous LD₅₀ = 8.6 mg kg⁻¹

Rabbit

ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)

ARfD - Acute Reference Dose (mg kg⁻¹ bw day⁻¹)

AAOEL - Acute Acceptable Operator Exposure Level (mg kg⁻¹ bw day⁻¹)

AOEL - Acceptable Operator Exposure Level - Systemic (mg kg⁻¹ bw day⁻¹)

Dermal penetration studies (%)

Dangerous Substances Directive 76/464

Exposure Routes

Public

Occupational

Mammalian dose elimination route and rate

Metabolised in the liver and eliminated in the urine with around 18% as the unchanged drug. Small amounts lost in bile and excreted in maternal milk in humans.

Health issues

Specific human health issues (hazard-based)

Carcinogen

Genotoxic

Endocrine disruptor

No data found

; ; ; ;

No data found

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

No data found

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

No data found

General human health issues

May lower blood pressure and cause drowsiness
CNS toxicant
May cause gastrointestinal changes

Handling issues

Property

Value and interpretation

General

No information available

CLP classification 2013

Health: H302, H318, H362, H370
Environment: H400, H410

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

amitriptyline

French

amitriptyline

German

Danish

Italian

Spanish

amitriptilina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	09/09/2025
Contact:	aeru@herts.ac.uk
Please cite as:	Lewis, K.A., Tzilivakis, J., Warner, D. and Green, A. (2016) An international database for pesticide risk assessments and management. Human and Ecological Risk Assessment: An International Journal, 22(4), 1050-1064. DOI: 10.1080/10807039.2015.1133242