Selegiline is a selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson’s disease. It may slow the progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon the onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.
Mechanism of action of Selegiline
Although the mechanisms for selegiline’s beneficial action in the treatment of Parkinson’s disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. Selegiline binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. Selegiline may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, selegiline can also inhibit monoamine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.
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The action of selegiline is thought to be related to its irreversible inhibition of monoamine oxidase type B (MAO B), the major form of the enzyme in the human brain. MAO B, which is involved in the oxidative deamination of dopamine in the brain, is inhibited when selegiline binds covalently and stoichiometrically to the isoalloxazine flavin adenine dinucleotide (FAD) at its active center. Administration of 10 mg of selegiline a day produces almost complete inhibition of MAO B in the brain. Selegiline becomes a nonselective inhibitor of all monoamine oxidase (MAO) at higher doses, possibly at 20 to 40 mg a day. At these doses, tyramine-mediated hypertensive reaction with MAO-A blockade (“cheese reactions”) may occur.
Indications of Selegiline
- Attention Deficit Disorder With Hyperactivity
- Depressive Disorder
- Parkinson’s Disease
- ADHD
- Depression
- Monotherapy for initial treatment of Parkinson’s disease, as well as an adjunct therapy in patients with a decreased response to levodopa/carbidopa. Also used for the palliative treatment of mild to moderate Alzheimer’s disease and at higher doses, for the treatment of depression.
Contra-Indications of Selegiline
- Malignant melanoma
- Severe mental disorder with loss of personality & reality
- Abnormal movements of facial muscles and tongue
- Abnormal heart rhythm
- Blood pressure drop upon standing
- Liver problems
- Kidney disease with the reduction in kidney function
- Allergies to monoamine oxidase inhibitors
Side Effects of Selegiline
The most common
- Dizziness
- Orthostatic hypotension
- Xerostomia (dry mouth)
- A headache
- Fatigue
- Skin reactions
- Hypotension
- Anxiety
- Constipation
- Sedation (dose-dependent)
- Nausea/vomiting
- Weight gain/loss
- Pain below the ear (from salivary gland)
- Erectile dysfunction
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- a cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- a headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions of Selegiline
Selegiline may interact with the following drug, supplements, & may change the efficacy of the drugs
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- atomoxetine
- cyclobenzaprine
- dextroamphetamine
- levodopa
- MAO inhibitors (e.g., phenelzine, tranylcypromine, rasagiline)
- beta-agonists (e.g., formoterol, salbutamol, salmeterol)
- other beta-blockers (e.g., propranolol, metoprolol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- cyclosporine
- dexamethasone
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide)
- duloxetine
- lapatinib
- levodopa
- sympathomimetic medications (e.g., pseudoephedrine, phenylephrine, ephedrine)
- tramadol
- lidocaine
- MAO inhibitors (e.g., phenelzine, moclobemide, )
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- nilotinib
- nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen)
- pentoxifylline
- phosphodiesterase-5-inhibitors (e.g., sildenafil, tadalafil)
- selective serotonin reuptake inhibitors (SSRI; e.g., fluoxetine, paroxetine, sertraline)
- tricyclic antidepressants (e.g., amitriptyline, doxepin, nortriptyline)
Pregnancy Catagory
FDA Pregnancy Category C
Pregnancy
This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if selegiline passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children.
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