Selegiline Hydrochloride

MAO-B Inhibitor Monoamine Oxidase Inhibitor (MAO-B selective)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.5-1 mg/kg (for PDH) or 0.5-1 mg/kg (for CDS) Once daily (q24h), preferably in the morning Duration: For PDH: lifelong; for CDS: at least 1-2 months to assess response, then continue if effective
Notes: For PDH, selegiline is only effective for pituitary-dependent (not adrenal-dependent) hyperadrenocorticism. For CDS, clinical improvement may take up to 8 weeks. Doses above 1 mg/kg may increase the risk of adverse effects and loss of MAO-B selectivity.
Cat PO Not established; not recommended N/A Duration: N/A
Notes: No approved use in cats. Safety and efficacy not established.
Horse PO Not established; not recommended N/A Duration: N/A
Notes: No approved use in horses. Some studies have used 0.5-1 mg/kg for PPID, but not standard.

Clinical Indications & Species Uses

General Indications
  • Selegiline is primarily used in dogs for PDH and CDS. It is not recommended for other species due to lack of safety and efficacy data.
Dog (Canine)
  • Pituitary-dependent hyperadrenocorticism (PDH) (Cushing's disease) – for uncomplicated cases
  • Canine cognitive dysfunction syndrome (CDS) – improvement of clinical signs such as disorientation, altered interactions, sleep-wake cycle disturbances, and house soiling

Pharmacology & Mechanism of Action

Drug Class: MAO-B Inhibitor | Pharmacological Group: Monoamine Oxidase Inhibitor (MAO-B selective)

Mechanism of Action: Selegiline is a selective, irreversible inhibitor of monoamine oxidase type B (MAO-B) at therapeutic doses. MAO-B is the enzyme primarily responsible for the oxidative deamination of dopamine in the brain. By inhibiting MAO-B, selegiline increases the concentration of dopamine in the synaptic cleft, thereby enhancing dopaminergic neurotransmission. It also has a mild amphetamine-like effect and may increase the release of dopamine and norepinephrine. In the brain, selegiline is metabolized to L-methamphetamine and L-amphetamine, which contribute to its stimulant effects. At higher doses, selectivity for MAO-B is lost, and it can also inhibit MAO-A, leading to increased levels of serotonin and norepinephrine, which may increase the risk of hypertensive crises if combined with tyramine-containing foods or other serotonergic drugs.

Pharmacodynamics: Selegiline produces its therapeutic effects by increasing dopaminergic activity in the central nervous system. In dogs with pituitary-dependent hyperadrenocorticism (PDH), selegiline is thought to act by increasing dopamine levels in the hypothalamus, which inhibits the secretion of adrenocorticotropic hormone (ACTH) from the pituitary, thereby reducing cortisol production. In canine cognitive dysfunction syndrome (CDS), selegiline improves cognitive function by enhancing dopaminergic neurotransmission in the cerebral cortex and hippocampus. The drug also has neuroprotective properties, possibly by reducing oxidative stress and preventing apoptosis of dopaminergic neurons. Clinical effects may take several weeks to become apparent, especially in CDS.

⚡ Pharmacokinetics Summary

Absorption: Selegiline is rapidly and well absorbed after oral administration in dogs. Peak plasma concentrations occur within 1-2 hours. Food may delay absorption but does not significantly affect overall bioavailability.
Distribution: Selegiline is highly lipophilic and distributes widely throughout the body, including the central nervous system. It crosses the blood-brain barrier readily. The volume of distribution is large, and it accumulates in tissues, particularly the brain and lungs.
Metabolism: Selegiline undergoes extensive hepatic metabolism, primarily via cytochrome P450 enzymes (CYP2B6, CYP3A4, and others). It is metabolized to N-desmethylselegiline, L-methamphetamine, and L-amphetamine, which are pharmacologically active. These metabolites contribute to the drug's effects and have longer half-lives than the parent compound.
Excretion: Selegiline and its metabolites are excreted primarily in the urine (about 70-80%) and to a lesser extent in feces. In dogs, the elimination half-life of selegiline is approximately 2-4 hours, but the active metabolites have half-lives of 12-20 hours, which allows for once-daily dosing.
Half-Life: Dog: 2-4 hours (parent drug); metabolites: 12-20 hours. Cat: not well documented, but similar to dog. Horse: not well documented.
Bioavailability: Oral bioavailability in dogs is approximately 10-20% due to extensive first-pass metabolism. However, the active metabolites contribute to the overall pharmacological effect.
Protein Binding: Selegiline is approximately 90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.

Available Formulations & Strengths

Oral Tablet 5 mg, 10 mg, 15 mg, 30 mg (PO)
Oral Capsule 5 mg, 10 mg (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to selegiline or any component of the formulation
  • Concurrent use of meperidine (pethidine) or other opioids (risk of serotonin syndrome)
  • Concurrent use of other MAO inhibitors (e.g., amitraz, tricyclic antidepressants, SSRIs) – washout period required
  • Use in animals with pheochromocytoma (risk of hypertensive crisis)
  • Use in animals with severe hepatic or renal impairment (caution, but not absolute contraindication)
Warnings & Clinical Precautions:
  • Use with caution in animals with a history of seizures, as selegiline may lower the seizure threshold.
  • Use with caution in geriatric animals, as they may be more sensitive to adverse effects.
  • Do not use in animals with hyperadrenocorticism caused by adrenal tumors (functional adrenal neoplasia) – selegiline is only effective for PDH.
  • Monitor for behavioral changes, especially increased anxiety or agitation.
  • In dogs with PDH, monitor cortisol levels and clinical signs regularly to assess response.
  • Avoid concurrent use with other serotonergic drugs (e.g., SSRIs, TCAs, tramadol) due to risk of serotonin syndrome. A washout period of at least 14 days is recommended when switching from or to these drugs.
  • Selegiline may cause mild stimulant effects; administer in the morning to avoid sleep disturbances.
  • In food animals, selegiline is not approved and must not be used due to lack of withdrawal times.

Adverse Effects & Reactions

Common:

  • Vomiting
  • Diarrhea
  • Decreased appetite
  • Lethargy
  • Restlessness or hyperactivity
  • Increased anxiety or agitation

Serious / Severe:

  • Serotonin syndrome (if combined with serotonergic drugs) – signs include agitation, tremors, hyperthermia, and seizures
  • Hypertensive crisis (especially if combined with tyramine-rich foods or sympathomimetics)
  • Seizures (in predisposed animals)
  • Hepatotoxicity (rare)

Rare:

  • Allergic reactions (skin rash, urticaria)
  • Blood dyscrasias
  • Behavioral changes (aggression, depression)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Meperidine (pethidine) and other opioids (e.g., tramadol, fentanyl) Risk of severe serotonin syndrome, CNS excitation, and hyperthermia. Contraindicated. High
Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, paroxetine) Risk of serotonin syndrome. Allow at least 14 days between discontinuation of one and initiation of the other. High
Tricyclic antidepressants (TCAs) (e.g., amitriptyline, clomipramine) Risk of serotonin syndrome and hypertensive crisis. Avoid concurrent use; washout period required. High
Sympathomimetics (e.g., ephedrine, phenylpropanolamine) Increased risk of hypertensive crisis and tachycardia. Moderate
Amitraz (used in collars or dips) Amitraz is an MAO inhibitor; concurrent use may lead to additive MAO inhibition and toxicity. High
Tyramine-rich foods (e.g., aged cheese, cured meats) At high doses, selegiline may lose MAO-B selectivity and inhibit MAO-A, leading to hypertensive crisis if tyramine is ingested. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Agitation
  • Hyperactivity
  • Tremors
  • Seizures
  • Hyperthermia
  • Tachycardia
  • Hypertension
  • Vomiting
  • Respiratory depression (in severe cases)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and the animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids for hydration and to maintain blood pressure. Control seizures with diazepam or barbiturates. Manage hyperthermia with cooling measures. Monitor cardiac function and blood pressure. There is no specific antidote for selegiline overdose. In severe cases, consider intensive care and monitoring.

Food Animal Withdrawal Times

Selegiline is not approved for use in food animals. Therefore, no withdrawal times have been established. Use in food animals is prohibited.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F).

Handling & Special Conditions: Protect from moisture. Keep in a tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: FDA-approved for use in dogs (Anipryl®) for the treatment of pituitary-dependent hyperadrenocorticism and canine cognitive dysfunction syndrome.

Extra-Label (Off-Label) Use: In the United States, selegiline is FDA-approved for use in dogs only. Extra-label use in other species is permitted under the Animal Medicinal Drug Use Clarification Act (AMDUCA) only if a valid veterinarian-client-patient relationship exists, and if the drug is not prohibited in food animals. However, selegiline is not approved for food animals, and its use in food animals is prohibited due to lack of withdrawal times.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Selegiline is a valuable therapeutic option for managing canine cognitive dysfunction syndrome and uncomplicated pituitary-dependent hyperadrenocorticism. It is generally well-tolerated, but clinical response may take several weeks. For PDH, it is essential to confirm the diagnosis as pituitary-dependent before initiating therapy, as it is ineffective for adrenal tumors. For CDS, selegiline may improve clinical signs, but it is not a cure; concurrent behavioral and environmental modifications are recommended. Due to the risk of serotonin syndrome, selegiline should not be combined with other serotonergic drugs, and a washout period is necessary. Monitoring for adverse effects, especially behavioral changes, is important. In geriatric dogs, start at the lower end of the dose range and titrate as needed. Selegiline is not recommended for use in cats or other species due to lack of safety and efficacy data.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)