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Selegiline for Dogs

By Barbara Forney, VMD

Last reviewed: 7/14/2022

Commonly prescribed for: Canine cognitive dysfunction, Cushing's Disease

Species: Dogs

Therapeutic Class: Monoamine Oxidase Inhibitor

Basic Information

Selegiline or L-Deprenyl is a centrally acting, selective, irreversible monamine oxidase-B (MAO-B) inhibitor that is FDA-approved for use in dogs for the treatment of canine cognitive dysfunction and pituitary-dependent Cushing’s disease. Selegiline is approved for use in humans as an adjunct for the treatment of Parkinson’s disease.

Monoamine oxidase inhibitors primarily act by increasing dopamine levels in the brain. Selegiline is metabolized into L-desmethylselegiline, amphetamine, and methamphetamine. All of these metabolites act as CNS stimulants. At higher doses selegiline also may inhibit MAO-A. Selegiline is primarily excreted in the urine.


Selegiline is the only FDA-approved treatment for canine cognitive dysfunction. Although the onset of action can be variable (between four and12 weeks), most dogs show some improvement after one month of treatment and there may be continued improvement over time. The neuroprotective effects of selegiline are thought to be due to increased dopamine levels. Selegiline does not cure canine cognitive dysfunction but can improve quality of life for both the pet and the owner. Selegiline has also been used off-label for cognitive dysfunction in the cat.

Selegiline is also approved for use in pituitary-dependent hyperadrenocorticism (PDH). It is less commonly used for the treatment of PDH as more recent research on efficacy has not been particularly supportive.

Side Effects

  • The more-common side effects include vomiting, diarrhea, and anorexia. If gastrointestinal side effects persist, discontinue the selegiline for a few days and re-start at a lower dose.
  • Side effects due to central nervous system stimulation include restlessness, hyperactivity, repetitive behaviors, and salivation.
  • Rare side-effects include deafness, pruritus, shivering, or trembling.
  • Additional side-effects reported in humans include hallucinations, insomnia, confusion, depression, and balance problems.


If selegiline is used to treat Cushing’s disease, appropriate diagnostic work-up should confirm that the hyperadrenocorticism is of pituitary, not adrenal, origin.

Drug Interactions

There are a number of potential drug interactions between MAO inhibitors in humans that may be of significance in the dog. There is very little specific veterinary information regarding these interactions. In human medicine, the recommended washout time for MAO inhibitor drugs and other drugs that may interact can be weeks.
  •  Amitraz is also a MAO inhibitor and should not be used with selegiline.
  • Selegiline should not be used with the following drugs due to the possibility of serotonin syndrome: bupropion, tramadol, tricyclic and tetracyclic anti-depressants (clomipramine, amitriptyline), selective serotonin re-uptake inhibitor (fluoxetine).
  • Ephedrine, pseudoephedrine, and phenylpropanolamine should not be used with selegiline. Possible hypertension and hyperpyrexia. A two-week separation period between these drugs has been suggested.
  • Opioids (especially meperidine) should not be used with selegiline. A two-week separation between these drugs has been suggested.


If acute overdose is recognized promptly, gut-emptying protocols may be of benefit.

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