SELERIN TABLETS

Indications

• Parkinson's disease
• Depression (at higher doses)

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: Initial: 5 mg taken once daily. Maximum: 10 mg per day.

Mechanism of action

Selegiline selectively and irreversibly inhibits monoamine oxidase type B (MAO-B), an enzyme responsible for the oxidative deamination of dopamine in the brain. This inhibition increases the availability of dopamine in the central nervous system, thereby enhancing its activity. At higher doses, selegiline may also inhibit monoamine oxidase type A (MAO-A), which is relevant for its antidepressant effects.

Pharmacodynamics

By selectively blocking MAO-B, selegiline prolongs the effects of dopamine in the brain, which is critical in managing Parkinson's disease. It reduces the premature degradation of dopamine, leading to improved motor function and reduced symptoms of the disease. Additionally, selegiline may enhance dopamine release from nerve cells and prevent dopamine reuptake between nerve endings.

Pharmacokinetics

Selegiline is absorbed rapidly after oral administration and undergoes extensive first-pass metabolism in the liver. It is metabolized to both active and inactive metabolites, which contribute to its therapeutic effects. The half-life of selegiline is relatively short, leading to the need for multiple daily doses to maintain effective plasma levels. It is primarily excreted in the urine as metabolites.

Interactions

• selegiline+opioids: Severe (increases risk of adverseeffects)
• selegiline+pethidine: Severe (increases risk of adverseeffects)

Pregnancy

Selegiline should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Selegiline should be used with caution during breastfeeding; it is not known if selegiline is excreted in human milk.

Storage

Store below 25 degrees Celsius. Protect from light and moisture.

Formulations

• Tablets
• Capsules

Indications

• Parkinson's disease, used alone or as an adjunct to levodopa or co-careldopa therapy to reduce 'end of dose' deterioration.
• Symptomatic parkinsonism.

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: Initially, 5 mg once daily for 2–4 weeks, then increased if tolerated to 10 mg daily, taken in the morning. Maximum daily dose should not exceed 50 mg in patients with moderate hepatic impairment.

Mechanism of action

Selegiline selectively inhibits monoamine oxidase B, an enzyme responsible for the degradation of dopamine in the brain. By inhibiting this enzyme, selegiline increases the availability of dopamine, which is crucial for the regulation of movement and coordination. This mechanism helps alleviate the symptoms of Parkinson's disease and enhances the effectiveness of levodopa therapy.

Pharmacodynamics

The pharmacodynamic effects of selegiline are primarily related to its action on the dopaminergic system. By preventing dopamine breakdown, selegiline increases dopamine levels in the synaptic cleft, contributing to improved motor function and reduction of 'end of dose' deterioration in patients with Parkinson's disease. It may also exhibit neuroprotective effects, potentially delaying the progression of the disease.

Pharmacokinetics

Selegiline is well-absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism, primarily in the liver, where it is converted to its active metabolites, including desmethylselegiline. The elimination half-life of selegiline is approximately 10 hours, but its metabolites may have longer-lasting effects. Selegiline is primarily excreted in urine as metabolites, with a small fraction excreted unchanged.

Contra-indications

• Active retinopathy
• Active duodenal ulceration
• History of severe hepatic impairment
• Hypertension
• Angina

Adverse effects

• Hypertension
• Dyskinesia
• Cognitive disorder
• Confusion
• Depression
• Gastrointestinal discomfort
• Dry mouth
• Diarrhea
• Constipation
• Emotional lability
• Psychosis
• Arrhythmias
• Dysarthria
• Dyslipidemia

Interactions

• Other MAO-B inhibitors
• Levodopa
• Antidepressants
• Sympathomimetics
• Alcohol

Precautions

• Caution in hepatic impairment
• Monitor blood pressure
• Avoid abrupt withdrawal
• Use with caution in patients with a history of confusion and psychosis

Pregnancy

Selegiline should not be used during pregnancy unless clearly necessary, as safety in human pregnancy has not been established.

Breast-feeding

Selegiline is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Oral tablets
• Oral lyophilisates
• Oral suspension

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.

Pharmacodynamics

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.