indication

Monotherapy for initial treatment of Parkinson's disease, as well as an adjunct therapy in patients with a decreased response to levodopa/carbadopa. Also used for the palliative treatment of mild to moderate Alzheimer's disease and at higher doses, for the treatment of depression.

pharmacology

Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine. Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO-B. It also may prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells.

mechanism of action

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 monozmine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.

toxicity

LD₅₀=63 mg/kg (rats, IV)

absorption

Rapidly absorbed from the gastrointestinal tract.

half life

1.2-2 hours

drug interactions

Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like selegiline.

Brimonidine: MAO Inhibitors like selegiline may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.

Buprenorphine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like selegiline. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Citalopram: Possible severe adverse reaction with this combination

Desvenlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Dextromethorphan: Combination associated with possible serotoninergic syndrome

Escitalopram: Possible severe adverse reaction with this combination

Fluoxetine: Possible severe adverse reaction with this combination

Fluvoxamine: Possible severe adverse reaction with this combination

Meperidine: Potentially fatal adverse effects

Moclobemide: Decrease in selectivity

Paroxetine: Possible severe adverse reaction with this combination

Tetrabenazine: Tetrabenazine may increase the adverse/toxic effects of Selegiline. Concomitant therapy is contraindicated.

Thiotepa: Thiotepa, a strong CYP2B6 inhibitor, may decrease the metabolism and clearance of Selegiline, a CYP2B6 substrate. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Selegiline if Thiotepa is initiated, discontinued or dose changed.

Tolcapone: Tolcapone and Selegiline decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.

Tramadol: Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Selegiline.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimipramine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Venlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Vilazodone: MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.

Zolmitriptan: The MAO inhibitor, selegiline, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing selegiline are contraindicated.