Pregabalin

Pregabalin	Last updated: 22/05/2024
(Not known by any other names)

GENERAL INFORMATION

Description

A neuroactive veterinary drug used for dedation and as an anticonvulsant

Availability status

Current

Introduction & key dates

Examples of veterinary uses

Used to assist with acute anxiety and fear associated with transportation and veterinary visits as well as treating epilepsy, chronic pain and seizures

Examples of species treated

Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Approved

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Substance is isomeric existing in the (R)- and (S)-forms. Pregabalin is the (S)-isomer and the potent of the two.

Chemical formula

C₈H₁₇NO₂

Canonical SMILES

CC(C)CC(CC(=O)O)CN

Isomeric SMILES

CC(C)C[C@@H](CC(=O)O)CN

International Chemical Identifier key (InChIKey)

AYXYPKUFHZROOJ-ZETCQYMHSA-N

International Chemical Identifier (InChI)

InChI=1S/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
(R)-pregabalin	Isomer
pregabalin	-
(S)-pregabalin	Isomer

General status

Veterinary substance type

Sedative

Substance groups

Alkylated analog of GABA

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Binds to the auxiliary subunit (alpha2-delta protein) of voltage-gated calcium channels in the CNS thereby reducing the release of various neurotransmitters and producing its anxiolytic effect.

Molecular targets

[Alpha2-delta subunits, Binder]

CAS RN

148553-50-8

EC number

604-639-1

CIPAC number

US EPA chemical code

PubChem CID

5486971

Therapeutic Class

Nervous system, other antiepileptics

ATCvet Code

QN03AX16

Controlled Drug?

UK: Class C, Schedule 3

Regulation 37/2010 MRL Classification

Molecular mass

159.23

PIN (Preferred Identification Name)

(3S)-3-(aminomethyl)-5-methylhexanoic acid

IUPAC name

(3S)-3-(aminomethyl)-5-methylhexanoic acid

CAS name

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white coloured crystalline solid

Formulations

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Example products (past and present) using this active

Bonqat 50 mg/ml oral solution for cats

Orion Corp

GB National authorisation

Prescription only medicine to be authorised by a veterinarian (POM-V)

Formulation and application details

Usually supplied as an oral solution

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

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

11300

High

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

Melting point (°C)

176

Boiling point (°C)

145

Degradation point (°C)

Flashpoint (°C)

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

2.00 X 10⁰¹

Calculated

Log P

1.3

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

4.2

pKa(2) = 10.6

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)

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)

> 5000

Rat

Low

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

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

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)

> 1000

Oncorhynchus mykiss

Low

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)

> 1000

Daphnia magna

Low

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 - Acute 7 day EC₅₀, biomass (mg l⁻¹)

Algae - Acute 72 hour EC₅₀, growth (mg l⁻¹)

Algae - Chronic 96 hour NOEC, growth (mg l⁻¹)

> 300

Scenedesmus quadricauda

Low

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves – Acute EC₅₀ development (mg l⁻¹)

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)

> 5000

Rat

Low

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

Pattern of use is unlikely to result in toxicological relevant exposure

Occupational

Pattern of use is unlikely to result in toxicological relevant exposure

Mammalian dose elimination route and rate

Elimination is primarily as an unchanged drug by renal excretion usually within 7 hrs

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

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

Originally approved in US as an anti-epileptic & anticonvulsant drug
May cause severe allergic reaction
Possible liver toxin

Handling issues

Property

Value and interpretation

General

Corrosive
Incompatible with strong oxidising agents

CLP classification 2013

Health: H373, H361, H318

WHO Classification

Not listed (Not listed)

UN Number

Not registered

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

Shelf-life for sale is 2 years but once package is opened shelf-life reduces to 6 months. Store in a refrigerator (2-8 DegC).

TRANSLATIONS

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English

pregabalin

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Record last updated:	22/05/2024
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