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 enzyme is predominantly found in the brain and is responsible for the catabolism of dopamine. By inhibiting MAO-B, selegiline reduces the breakdown of dopamine, leading to increased levels of this neurotransmitter in the synaptic cleft. This action is particularly beneficial in conditions like Parkinson's disease, where dopamine levels are critically low.

Pharmacokinetics

Selegiline is well absorbed from the gastrointestinal tract when administered orally. It undergoes extensive first-pass metabolism in the liver, resulting in the formation of several metabolites, including L-amphetamine and L-methamphetamine, which may contribute to its pharmacological effects.

Metabolism

Metabolic pathway of selegiline

The metabolism of selegiline involves N-dealkylation and hydroxylation, primarily by the cytochrome P450 enzymes CYP2B6 and CYP2C19. The primary metabolites, L-amphetamine and L-methamphetamine, are further metabolized and excreted in the urine. These metabolites have been suggested to contribute to the therapeutic effects of selegiline, although their exact role remains a subject of research.

Clinical Uses

Selegiline is primarily used in the management of Parkinson's disease, often as an adjunct to levodopa therapy. It helps to prolong the effects of levodopa by preventing the breakdown of dopamine. Additionally, selegiline is used in the treatment of major depressive disorder, particularly in its transdermal form, which bypasses the gastrointestinal tract and reduces the formation of amphetamine-like metabolites.

Side Effects

Common side effects of selegiline include nausea, dizziness, abdominal pain, and dry mouth. Due to its metabolism to amphetamine derivatives, it may also cause insomnia and increased heart rate. At higher doses, selegiline loses its selectivity for MAO-B and may inhibit MAO-A, leading to potential interactions with tyramine-containing foods and the risk of hypertensive crisis.

Drug Interactions

Selegiline can interact with a variety of medications, including other MAO inhibitors, SSRIs, and tricyclic antidepressants. These interactions can lead to serious conditions such as serotonin syndrome. It is important to monitor patients closely when selegiline is used in combination with other medications affecting the central nervous system.

Related Pages

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