Tramadol

Tramadol	Last updated: 12/09/2025
(Not known by any other names)

GENERAL INFORMATION

Description

A synthetic codine analogue used in veterinary medicine which is usually formulated as the hydrochloride salt.

Examples of veterinary uses

Used to control acute and chronic pain of moderate to severe intensity

Examples of species treated

Dogs

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved - usually supplied as a prescription only medicine to be authorised by a veterinarian (POM-V)

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Tramadol exhibits stereoisomerism, specifically enantiomerism, due to the presence of two chiral centres in its cyclohexanol structure. The marketed drug is a racemic mixture of (+)-cis-(1R,2R)-tramadol and (–)-cis-(1S,2S)-tramadol. The (–)-enantiomer is more active in norepinephrine reuptake inhibition than the (+)-enantiomer. In addition, tramadol is metabolised into O-desmethyltramadol, which itself has stereoisomers and is a much more potent mu-opioid agonist, further complicating its pharmacodynamics.

Chemical formula

C₁₆H₂₅NO₂

Canonical SMILES

CN(C)CC1CCCCC1(C2=CC(=CC=C2)OC)O

Isomeric SMILES

CN(C)C[C@H]1CCCC[C@@]1(C2=CC(=CC=C2)OC)O

International Chemical Identifier key (InChIKey)

TVYLLZQTGLZFBW-ZBFHGGJFSA-N

International Chemical Identifier (InChI)

InChI=1S/C16H25NO2/c1-17(2)12-14-7-4-5-10-16(14,18)13-8-6-9-15(11-13)19-3/h6,8-9,11,14,18H,4-5,7,10,12H2,1-3H3/t14-,16+/m1/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
tramadol hydrochloride	Variant

General status

Veterinary substance type

Medicinal drug: Analgesic

Substance groups

Opoid

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Multiple activity routes

Molecular targets

[µ-opioid receptor, Agonist], [Sodium-dependent noradrenaline transporter, Inhibitor], [Sodium-dependent serotonin transporter, Inhibitor], [5-hydroxytryptamine receptor 2C, Antagonist], [Kappa-type opioid receptor, Agonist], [Delta-type opioid receptor, Agonist]

CAS RN

27203-92-5

EC number

248-319-6

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Nervous system: Other opioids

ATCvet Code

QN02AX02

Controlled Drug?

UK: Class C, Schedule 3

Regulation 37/2010 MRL Classification

Molecular mass

263.38

PIN (Preferred Identification Name)

2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol

IUPAC name

(1R,2R)-2-((dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexan-1-ol

CAS name

(+/-)-cis-(2-dimethylaminomethyl)-1-(3-methoxyphenyl)-cyclohexanol

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Related substances & organisms

tramadol hydrochloride

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1977, launched Germany; 1962, first synthesised

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

Chanelle Pharmaceuticals Manufacturing Ltd

Example products using this active

Tramvetol

Formulation and application details

Usually supplied in tablet for oral administration. Human brands also used for animals, off-label

Commercial production

Tramadol is synthesised through a multi-step chemical process that begins with cyclohexanone as the core starting material. The first major step involves a Mannich reaction, where cyclohexanone reacts with dimethylamine and formaldehyde to introduce a dimethylaminomethyl group at the alpha position. This intermediate is then coupled with meta-methoxyphenyl magnesium bromide (a Grignard reagent), forming the key aryl-substituted cyclohexanol structure. The resulting mixture contains both cis and trans isomers, but the trans isomer (RR,SS) is pharmacologically active and is selectively converted into tramadol hydrochloride by reacting with hydrochloric acid in the presence of a small amount of water. Modern production methods often use continuous-flow synthesis to improve efficiency, safety, and scalability, allowing for precise control over reaction conditions and purification.

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)

39.5

Moderate

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

Melting point (°C)

180

as the HCl salt

Boiling point (°C)

Degradation point (°C)

Flashpoint (°C)

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

2.24 X 10⁰¹

Calculated

Log P

1.35

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

9.41

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

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 soil and groundwater metabolites

None

Other known metabolites

Metabolite name and reference

Aliases

Formation medium / Rate

Estimated maximum occurrence fraction

O-desmethyltramadol

Human liver

N-desmethyltramadol

Human liver

O-desmethyl-tramado glucuronide

Human liver

N,O-didesmethyltramadol

Human liver

N,N-didesmethyltramadol

Human liver

N,N,O-tridesmethyl-tramadol

Human liver

N,N,O-tridesmethyl-tramadol

Human liverl

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

350

Mouse

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)

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

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)

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)

350

Mouse

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Intraperitoneal LD₅₀ = 150 mg kg⁻¹

Rat

Subcutaneous LD₅₀ = 286 mg kg⁻¹

Rat

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

Extensively metabolised in the liver (0% eliminated in the urine, 10% in faeces)

Health issues

Specific human health issues

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

CNS depressant
May depress respiratory function
Some incidences of adverse reactions recorded including headache, diarrhoea, vomiting & cardiovascular irregularities

Handling issues

Property

Value and interpretation

General

Will emit toxic fumes when heated to decomposition

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

tramadol

French

German

Danish

Italian

Spanish

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	12/09/2025
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