Pharmacology of selegiline

Pharmacological properties of selegiline

Introduction

Chemical structure of selegiline

Selegiline, also known as L-deprenyl, is a medication primarily used in the treatment of Parkinson's disease and major depressive disorder. It is a selective, irreversible inhibitor of monoamine oxidase B (MAO-B), an enzyme responsible for the breakdown of dopamine in the brain. By inhibiting this enzyme, selegiline increases the availability of dopamine, thereby alleviating symptoms associated with dopamine deficiency.

Mechanism of Action

Selegiline exerts its effects by selectively inhibiting the MAO-B enzyme. This inhibition prevents the breakdown of dopamine, leading to increased levels of this neurotransmitter in the central nervous system. At higher doses, selegiline can also inhibit monoamine oxidase A (MAO-A), which affects the metabolism of other neurotransmitters such as serotonin and norepinephrine.

Pharmacokinetics

Selegiline is well absorbed from the gastrointestinal tract, but it undergoes extensive first-pass metabolism in the liver. The drug is metabolized into several active metabolites, including amphetamine and methamphetamine, which may contribute to its therapeutic and side effects.

Metabolism of selegiline

The primary route of elimination is through the urine, with a smaller amount excreted in the feces. The half-life of selegiline is approximately 10 hours, but its metabolites can have longer half-lives, extending the duration of its effects.

Clinical Uses

Selegiline is primarily used in the management of Parkinson's disease, often as an adjunct to levodopa therapy. It helps to reduce the "off" periods associated with levodopa treatment. In addition, selegiline is used in the treatment of major depressive disorder, particularly in its transdermal patch form, which allows for higher systemic exposure without significant inhibition of MAO-A in the gut.

Side Effects

Common side effects of selegiline include nausea, dizziness, abdominal pain, and dry mouth. Due to its metabolism to amphetamine-like compounds, it can also cause insomnia and increased heart rate. At higher doses, the risk of hypertensive crisis increases, especially if dietary restrictions on tyramine are not followed.

Drug Interactions

Selegiline can interact with a variety of medications, including other MAO inhibitors, selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants. These interactions can lead to serious conditions such as serotonin syndrome or hypertensive crisis. It is important to monitor patients closely and adjust dosages accordingly.

Related Pages

• Monoamine oxidase inhibitor
• Parkinson's disease
• Dopamine
• Antidepressant