Clomipramine hydrochloride

Clomipramine hydrochloride	Last updated: 06/09/2025
(Also known as: clomipramine HCl ; monochlorimipramine HCl; 3-chloroimipramine hydrochloride)

GENERAL INFORMATION

Description

A veterinary anxiety drug

Examples of veterinary uses

Widely used for the treatment of disturbed behaviour such as urine spraying or fealther pulling

Examples of species treated

Cats; Dogs; Horses; Pet birds

Approval status

VMR 2013/2033 approval status (GB/UK)

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

EU Regulatory approval status

Approved

Chemical structure

Isomerism

Clomipramine hydrochloride exhibits geometric (cis-trans or E/Z) isomerism, primarily due to the presence of a double bond in its tricyclic structure that allows for restricted rotation. The molecule contains a dibenzazepine ring system with a side chain that includes a dimethylaminopropyl group, and the spatial arrangement around this system can give rise to different isomers. Specifically, clomipramine can exist in (E)- and (Z)-isomeric forms, which differ in the relative positions of substituents across the double bond.

Chemical formula

C₁₉H₂₄Cl₂N₂

Canonical SMILES

CN(C)CCCN1C2=CC=CC=C2CCC3=C1C=C(C=C3)Cl.Cl

Isomeric SMILES

International Chemical Identifier key (InChIKey)

WIMWMKZEIBHDTH-UHFFFAOYSA-N

International Chemical Identifier (InChI)

InChI=1S/C19H23ClN2.ClH/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22;/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3;1H

2D structure diagram/image available?

Yes

General status

Veterinary substance type

Antidepressant, Medicinal drug

Substance groups

Unclassified substance

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Largely unclear but though to inhibit norepinephrine and serotonin uptake into central nerve terminals

Molecular targets

[Sodium-dependent serotonin transporter, Antagonist], [5-hydroxytryptamine 2A receptor, Antagonist], [5-hydroxytryptamine 2B receptor, Antagonist], [5-hydroxytryptamine 2C receptor, Antagonist], [Sodium-dependent noradrenaline transporter, Antagonist], [Glutathione S-transferase P, Antagonist]

CAS RN

17321-77-6

EC number

241-344-3

CIPAC number

US EPA chemical code

PubChem CID

68539

Therapeutic Class

Nervous system: Psychoanaleptics

ATCvet Code

QN06AA04

Controlled Drug?

Regulation 37/2010 MRL Classification

Molecular mass

351.32

PIN (Preferred Identification Name)

IUPAC name

3-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine monohydrochloride

CAS name

5H-dibenz(b,f)azepine-5-propanamine, 3-chloro-10,11-dihydro-N,N-dimethyl-, monohydrochloride

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

Off-white coloured solid

Commercial

Property

Product

Manufacturer

Authorisation Route

Legal Class (GB/UK)

Availability status

Current

Introduction & key dates

circa 1960s, discovered

Example products (past and present) using this active

Clomicalm tablets for dogs

Virbac

GB National authorisation

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

Formulation and application details

Usually supplied tablet form for oral administration

Commercial production

The production of clomipramine hydrochloride involves a multi-step synthetic process starting with iminodibenzyl, which serves as the tricyclic core. This compound undergoes chlorination to introduce a chlorine atom at the 3-position, forming 3-chloroiminodibenzyl. Next, a side-chain alkylation is performed using 3-dimethylaminopropyl chloride, attaching the dimethylaminopropyl group via nucleophilic substitution. The resulting base is then treated with hydrochloric acid to form the hydrochloride salt, enhancing its solubility and stability for pharmaceutical use.

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)

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

Melting point (°C)

189

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

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

desmethylclomipramine

Humans (Liver)

8-hydroxyclomipramine

clomipramine N-oxide

2-hydroxyclomipramine

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

470

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)

High (class III)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

470

Mouse

Moderate

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

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 1750 mg kg⁻¹

Rat

Intravenous LD₅₀ = 26 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

Around 50-60% of administered dose is elminated in the urine and about 20-30% in faeces. Also found in human milk

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

No data found

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

No data found

Eye irritant

Phototoxicant

General human health issues

May cause fatigue, dizziness, lightheadedness, headaches, confusion, agitation and various other side effects

Handling issues

Property

Value and interpretation

General

No information available

CLP classification 2013

WHO Classification

Not listed (Not listed)

UN Number

Not regulated

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

clomipramine hydrochloride

French

German

Danish

Italian

Spanish

clomipramina

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	06/09/2025
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