Selegiline is a prescription medication classified as a monoamine oxidase inhibitor (MAOI), primarily used in the management of certain neurological conditions. It functions by affecting the levels of specific chemical messengers, known as monoamines, in the brain. The drug is available in oral forms, such as tablets and orally disintegrating tablets, and also as a transdermal patch, with the route of administration often depending on the medical condition being treated.
Understanding How Selegiline Works
The mechanism of action for selegiline involves its ability to irreversibly inhibit the monoamine oxidase (MAO) enzyme system in the brain. MAO enzymes break down monoamine neurotransmitters, including dopamine, serotonin, and norepinephrine. There are two main forms of this enzyme, MAO-A and MAO-B, which metabolize different neurotransmitters.
At the typical low doses prescribed for neurological movement disorders, selegiline selectively targets and inactivates the MAO-B enzyme. MAO-B is primarily responsible for breaking down dopamine. By blocking MAO-B, selegiline prevents the premature destruction of dopamine, increasing its concentration and duration of action in the synaptic spaces.
When administered at higher doses, selegiline loses its MAO-B selectivity and begins to inhibit MAO-A as well. This dual inhibition affects the metabolism of serotonin and norepinephrine in addition to dopamine, which is relevant to its use in treating mood disorders.
Approved Medical Applications
Selegiline is approved for two distinct medical conditions, with the formulation often tailored to the specific indication. The primary application is in the management of Parkinson’s Disease (PD), addressing the progressive loss of dopamine-producing neurons. It can be used as initial monotherapy for patients with mild early-stage PD to manage motor symptoms without immediately starting levodopa therapy.
Selegiline is more commonly employed as an adjunctive treatment alongside levodopa and carbidopa in patients with advanced PD. Adding selegiline extends levodopa’s effectiveness by slowing its breakdown. This helps manage the “wearing-off” periods that occur between doses, allowing for a more consistent supply of dopamine to the brain and smoothing out motor fluctuations.
The second approved application is the treatment of major depressive disorder (MDD) in adults. For MDD, selegiline is typically administered via a transdermal patch system. Patch delivery bypasses the digestive system and liver metabolism, allowing for effective inhibition of both MAO-A and MAO-B in the central nervous system. This broader inhibition increases the levels of serotonin and norepinephrine required for an antidepressant effect.
Managing Potential Adverse Reactions
Patients taking selegiline may experience a range of side effects, with some being common and generally manageable. Among the most frequently reported common adverse reactions are nausea, dry mouth, and dizziness. Gastrointestinal issues like constipation or abdominal pain are also sometimes noted.
Insomnia is another common reaction, likely due to selegiline’s amphetamine-like metabolites. This can often be mitigated by ensuring the final daily dose is taken before mid-afternoon. Orthostatic hypotension, a sudden drop in blood pressure upon standing that causes lightheadedness or fainting, is another important reaction.
More serious adverse reactions require prompt consultation with a healthcare provider. These include mental status changes such as confusion, hallucinations, and psychotic-like behavior, especially in older patients or those taking higher doses. When used with levodopa, selegiline can increase the occurrence of involuntary movements known as dyskinesia. If this occurs, the levodopa dosage may need to be adjusted downward to reduce the severity of these movements.
Patients should also be aware of the potential for sudden sleep episodes or excessive drowsiness while engaging in daily activities. Monitoring for changes in impulse control is advised, as some individuals may experience intense urges, such as increased gambling or sexual urges. Any severe headache, stiff neck, or chest pain must be reported immediately, as these can be signs of a serious hypertensive reaction.
Critical Drug and Dietary Interactions
A significant concern with selegiline, as with all MAO inhibitors, is the potential for dangerous drug and dietary interactions. The most important drug interaction involves combining selegiline with other medications that increase serotonin levels in the brain. This can lead to Serotonin Syndrome, a severe reaction characterized by agitation, confusion, rapid heart rate, high blood pressure, and muscle rigidity.
Serotonin Syndrome is a high risk when combining selegiline with serotonergic agents, including:
- Selective serotonin reuptake inhibitors (SSRIs)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
- Tricyclic antidepressants (TCAs)
- Certain pain medications like meperidine and tramadol
A “washout period” of at least 14 days is typically required when switching between selegiline and these medications. Over-the-counter cough and cold medicines containing dextromethorphan must also be avoided due to the potential for dangerous interaction.
The most well-known dietary concern with MAO inhibitors is the risk of a hypertensive crisis from consuming foods rich in tyramine. Tyramine is a substance found in aged, fermented, or cured foods, such as aged cheeses, cured meats, sauerkraut, and draft beers. Normally, MAO-A in the gut breaks down this tyramine, preventing it from entering the bloodstream and causing a sudden, severe elevation in blood pressure.
While oral selegiline is generally selective for MAO-B at low doses, its selectivity is not absolute, and rare cases of hypertensive crisis have been reported with high tyramine intake. The transdermal patch formulation at the lowest dose (6 mg/24 hours) is designed to minimize MAO-A inhibition in the gut, often allowing patients to use it without strict dietary restrictions. However, patients using higher dose patches or high-dose oral selegiline must still follow a modified diet to avoid foods with high tyramine content.