Amantadine

Amantadine	Last updated: 09/09/2025
(Also known as: 1-aminoadamantane)

GENERAL INFORMATION

Description

A veterinary drug used as an antiviral agent and/or as pain relief often used in conjunction with NSAIDs or opiods

Examples of veterinary uses

Used as an antiviral agent and/or as pain relief caused by conditions such as arthritis and cancer

Examples of species treated

Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Amantadine exhibits structural isomerism, particularly due to the position of its amino group on the adamantane cage. The adamantane structure is a rigid, tricyclic hydrocarbon resembling a diamond-like cage, and the amino group can attach at different carbon positions, most notably at the 1-position or 2-position, giving rise to 1-aminoadamantane (amantadine) and 2-aminoadamantane, respectively. Studies have shown that protonation of amantadine can lead to open-cage iminium isomers, where the adamantane framework partially opens under certain conditions, forming less stable but distinct species. While amantadine itself does not exhibit stereoisomerism due to its symmetrical cage, its derivatives and protonated forms introduce more complex isomeric behaviour relevant to pharmaceutical applications.

Chemical formula

C₁₀H₁₇N

Canonical SMILES

C1C2CC3CC1CC(C2)(C3)N

Isomeric SMILES

No data

International Chemical Identifier key (InChIKey)

DKNWSYNQZKUICI-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C10H17N/c11-10-4-7-1-8(5-10)3-9(2-7)6-10/h7-9H,1-6,11H2

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
amantadine	-

General status

Veterinary substance type

Medicinal drug: Antiviral agent, Pain relief

Substance groups

Unclassified substance

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Inhibits viral replication by interfering with an integral membrane protein

Molecular targets

[Matrix protein 2, Inhibitor], [Glutamate receptor ionotropic, NMDA 3A, Antagonist], [D(2) dopamine receptor, Agonist], [Aromatic-L-amino-acid decarboxylase, Inducer]

CAS RN

768-94-5

EC number

212-201-2

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Nervous system: Adamantane derivatives

ATCvet Code

QN04BB01

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

151.25

PIN (Preferred Identification Name)

adamantan-1-amine

IUPAC name

adamantan-1-amine

CAS name

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Related substances & organisms

amantadine hydrochloride

amantadine sulphate

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1966, first introduced USA as human drug to treat Asian influenza

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

Endo Pharmaceuticals

Example products using this active

Symmetrel

Formulation and application details

Usually supplied and administered either as tablets or as a liquid oral solution.

Commercial production

The production of amantadine typically begins with 1-bromoadamantane, a halogenated derivative of adamantane. In one efficient method, this compound is reacted with formamide to produce N-(1-adamantyl)formamide, a key intermediate. This step is carried out under mild conditions with high yield, often using a phase transfer catalyst like tetrabutylammonium iodide to enhance reaction efficiency. The intermediate is then subjected to acidic hydrolysis, usually with aqueous hydrochloric acid, which cleaves the formamide group and yields amantadine 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)

5200

High

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

6290

Melting point (°C)

Boiling point (°C)

136.1

Degradation point (°C)

Flashpoint (°C)

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

2.75 X 10⁰²

Calculated

Log P

2.44

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

0.894

Dissociation constant pKa) at 25 °C

10.45

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 metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

890

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)

> 22.6

Pimephales promelas

Moderate

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)

> 17.4

Daphnia magna

Moderate

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) (EC₅₀)

30.8

Desmodesmus subspicata

Low

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

62.1

Desmodesmus subspicata

Low

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)

890

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

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

Rapidly and almost completely absorbed from gastrointestinal tract. Unmetabolised renal elimination (90%)

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 cause nervousness, irritability, or insomnia, and possibly seizures
May cause nausea, constipation or diarrhoea, dry mouth, and loss of appetite
May cause serious eye and skin damage if in contact

Handling issues

Property

Value and interpretation

General

Flammable
Corrosive

CLP classification 2013

Health: H302, H312, H314, H318, H335, H361fd
Handling: H226

WHO Classification

Not listed (Not listed)

UN Number

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

amantadine

French

German

Danish

Italian

Spanish

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