Imipramine
Imipramine hydrochloride, Imipramine pamoate
Also known as: Tofranil-PM · imipramini chloridum · imipramini hydrochloridum · imizine · Antidep · Celamine · Depramina · Depsonil · Elepsin · Ethipramine · Imiprex · Imiprin · Imp-Tab · Impril · Janimine · Melipramine · Mipralin · Novo-Pramine · Praminan · Primonil · Pryleugan · Sermonil · Surplix · Talpramin · Imipraminum
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Urethral incompetence | 5-15 mg (total dose) | PO | q12h | — | 🌎 NA |
| Urinary incontinence when other agents fail | 5-20 mg (total dose) | PO | q12h | — | 🌎 NA |
| Cataplexy | 0.5-1 mg/kg | PO | q8h | — | 🌎 NA |
| Adjunctive treatment of separation anxiety or other tricyclic antidepressant-responsive behavior disorders | 2.2-4.4 mg/kg | PO | once to twice daily | — | 🌎 NA |
| Adjunctive cancer pain treatment | 0.5-1 mg/kg | PO | q8h | — | 🌎 NA |
| Anxiety, inappropriate urination, narcolepsy | 1-2 mg/kg | PO | q12h | — | 🌍 EU |
| Anxiety, inappropriate urination, narcolepsy | 2-4 mg/kg | PO | q24h | — | 🌍 EU |
- Cataplexy: Titrate dose based on clinical effect
- Anxiety, inappropriate urination, narcolepsy: Alternatively, 2-4 mg/kg p.o. q24h
- Anxiety, inappropriate urination, narcolepsy: Alternatively, 1-2 mg/kg p.o. q12h
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Urethral incompetence | 2.5-5 mg (total dose) | PO | q12h | — | 🌎 NA |
| Adjunctive cancer pain treatment | 2.5-5 mg (total dose) | PO | q12h | — | 🌎 NA |
| Anxiety, inappropriate urination | 0.5-1 mg/kg | PO | q12-24h | — | 🌍 EU |
Horses
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Pharmacologic induced ejaculation | 2 mg/kg | IV | once | — | 🌎 NA |
| Narcolepsy/cataplexy | 0.55 mg/kg IV or 250-750 mg (total dose) orally | IV, PO | once | — | 🌎 NA |
- Pharmacologic induced ejaculation: If imipramine alone does not induce erection and ejaculation in 10-15 minutes, give xylazine 0.2-0.3 mg/kg IV. (Note: ARCI UCGFS Class 2 Drug)
- Narcolepsy/cataplexy: PO administration produces inconsistent results.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Imipramine is a tricyclic antidepressant (TCA) used off-label in veterinary medicine. While primarily recognized for its behavioral applications (such as separation anxiety), its unique receptor profile makes it highly versatile.
- In dogs and cats, it is frequently utilized for urinary incontinence (urethral incompetence) and cataplexy.
- In equine medicine, it is employed to manage narcolepsy and to induce pharmacologic ejaculation.
Clinical Pearl: Imipramine is a tertiary amine TCA that is rapidly metabolized in the liver into its active secondary amine metabolite, desipramine. This dual-action broadens its pharmacologic spectrum, affecting both serotonin and norepinephrine pathways.
Mechanism of action
Imipramine and its active metabolite, desipramine, exert their effects through a complex, multi-receptor pharmacologic profile:
- Monoamine Reuptake Inhibition: Blocks the presynaptic amine pump, preventing the reuptake of serotonin (5-HT) and norepinephrine (NE) → increases neurotransmitter concentrations in the synaptic cleft → modulates mood, arousal, and pain pathways.
- Anticholinergic Activity: Antagonizes muscarinic receptors centrally and peripherally. This mechanism is primarily responsible for its efficacy in treating urinary incontinence (facilitating urine storage by relaxing the detrusor muscle) and its common side effects (dry mouth, tachycardia).
- Alpha-Adrenergic Agonism/Antagonism: Exhibits complex interactions at alpha receptors, which may contribute to increasing internal urethral sphincter tone.
- Antihistaminic (H1) Activity: Contributes to its significant sedative properties.
Safety & warnings
Contraindications
- Prior sensitivity to any tricyclic antidepressant
- Concomitant use with monoamine oxidase inhibitors (MAOIs) within 14 days
- Glaucoma
- History of seizures
- Urinary retention
- Severe liver disease
- Hypersensitivity to tricyclic antidepressants
Adverse effects
- Sedation
- Dry mouth
- Constipation
- Tachycardia
- Hyperexcitability
- Tremors
- Seizures (CNS stimulation)
- Bone marrow suppression
- Diarrhea
- Vomiting
- Diarrhoea
- Arrhythmias
- Hypotension
- Syncope
- Increased appetite
Precautions
Use with extreme caution in patients with seizure disorders, as imipramine may lower the seizure threshold.
Pregnancy Warning: There are isolated reports of limb reduction abnormalities (teratogenic potential). Restrict use in pregnant animals to situations where benefits clearly outweigh the risks (FDA Category D in humans).
Nursing: Excreted into milk in low concentrations (milk:plasma ratio 0.4 to 1.5).
Drug interactions
Additive anticholinergic effects; use cautiously
May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity
Additive CNS depressant effects; use cautiously
Imipramine may decrease levodopa oral absorption
May decrease tricyclic levels
Increased risk for QTc interval prolongation and tricyclic adverse effects
May decrease tricyclic blood levels
Increased risk for serotonin syndrome
May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia)
Concomitant use (within 14 days) is generally contraindicated due to risk of serotonin syndrome
May increase risk for cardiac arrhythmias
Increased risk for prolonged QT interval
Tricyclics may increase blood pressure
High risk of fatal serotonin syndrome
Altered metabolism via cytochrome P450 2D6 competition/inhibition
Increased risk of serotonin syndrome
Increased risk of serotonin syndrome (use only in exceptional cases with careful monitoring)
Monitoring
- Clinical efficacy
- Adverse effects
- ECG (Tricyclics can widen QRS complexes, prolong PR intervals, and invert or flatten T-waves)
- Blood Glucose (Tricyclics may increase or decrease blood glucose levels)
- Heart rate and rhythm (ECG) in susceptible patients
- Signs of serotonin syndrome (agitation, tremors, hyperthermia, tachycardia) if used with other serotonergic drugs
- Liver function tests (baseline and periodic)
Pharmacokinetics
Absorption
Rapidly absorbed from both the GI tract and parenteral injection sites. Peak levels occur within 1-2 hours after oral dosing.
Distribution
Enters the CNS and maternal milk in levels equal to that found in maternal serum.
Metabolism
Metabolized in the liver to several metabolites, including the active metabolite desipramine.
Overdose
Overdosage with tricyclics can be life-threatening, leading to severe arrhythmias and cardiorespiratory collapse. Because the toxicities and therapies for treatment are complicated and controversial, it is highly recommended to contact a poison control center for further information in any potential overdose situation.
Available products
Formulations
- Tablets
- Capsules
- Injection (Note: The injectable product is no longer marketed in the USA)
- 10 mg oral tablet
- 25 mg oral tablet
Human-labeled
- Imipramine HCl Tablets: 10 mg, 25 mg & 50 mg (Tofranil, generic)
- Imipramine Pamoate Capsules: 75 mg, 100 mg, 125 mg & 150 mg (Tofranil-PM, generic)
- Tofranil 10 mg tablets
- Tofranil 25 mg tablets
- Imipramine 10 mg tablets
- Imipramine 25 mg tablets
Regulatory status
POM. Veterinary authorized products (e.g., clomipramine) are preferred under the cascade.
POM. Veterinary authorized products (e.g., clomipramine) are preferred under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Imipramine HCl tablets and pamoate capsules should be stored in tight, light-resistant containers, preferably at room temperature. The HCl injection should be stored at < 40°C; avoid freezing. Imipramine HCl will turn yellow to reddish on exposure. Slight discoloration will not affect potency, but marked changes in color are associated with a loss of potency.
Client information
- Patience is Key: Behavioral changes may take several weeks to become noticeable. Continue dosing as prescribed and do not stop the medication abruptly without consulting your veterinarian.
- Safety First: This medication is highly toxic in overdose to both animals and humans. Keep it in child-resistant packaging, securely locked away from pets and children.
- Side Effects: You may notice your pet becoming sleepy, having a dry mouth, or experiencing constipation. If your pet seems overly excited, trembles, or has a seizure, contact your vet immediately.
- Missed Doses: If you miss a dose, give it when you remember, but never double up on doses.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.