Selegelin is a drug in the monoamine oxidase inhibitor (MAO-B inhibitor ) drug class. The antiparkinsonian drug inhibits the breakdown of dopamine in the brain.
What is selegelin?
Selegelin is used to treat Parkinson’s disease. Selegelin is used to treat Parkinson’s disease. Because of its short half-life, and therefore weak effect, it is usually given in combination with the drug levodopa. In milder disease courses, it can also be used as a monotherapeutic. In the United States, the active ingredient is also used for the treatment of depression. Selegelin is an MAO-B inhibitor. It inhibits the enzyme monoaminooxidase B. The drug was discovered by the chemist József Knoll. The production of selegelin requires a multi-step synthesis. This starts from (RS)-methamphetamine.
Pharmacological action
The cause of Parkinson’s disease is the death of special nerve cells in the substantia nigra. These nerve cells normally release dopamine. When the dopamine-releasing nerve cells perish, a dopamine deficiency occurs. It has not yet been determined why the cells perish. Dopamine is a neurotransmitter needed for the proper execution of movement. The body can compensate for the lack of dopamine for a long time. The first symptoms do not appear until 60 percent of the dopamine-producing nerve cells have died. To slow the progress of the disease and alleviate its symptoms, patients receive dopamine in the form of the precursor L-dopa. Since the dopamine formed from L-dopa is already broken down in the synaptic cleft between the nerve cells by the enzyme monoaminooxidase B, this enzyme must be inhibited. Otherwise, the dopamine supplied cannot exert its effect at the target site. Selegelin is such a monoaminooxidase B inhibitor. It ensures irreversible inhibition of MAO-B. As a result, dopamine remains longer in the synaptic cleft and can thus exert its full effect in the central nervous system.
Medical application and use
Selegelin is approved as a monotherapeutic agent for the treatment of the early stages of Parkinson’s disease. In combination with the drug levodopa, selegelin is used for symptomatic therapy of Parkinson’s disease. The drug is primarily administered to patients with a so-called fluctuating clinical picture. This is manifested, for example, by the on-off phenomenon. In this case, the patient experiences a sudden change from normal mobility to complete immobility. End-of-dose akinesias are another sign of a fluctuating clinical picture. These fluctuations in mobility may occur after prolonged use of L-dopa. The fluctuations in mobility are caused by a lessening of the drug’s effect. Selegelin can mitigate these fluctuations. In the USA, Selegelin is prescribed for the treatment of depression. In Germany, the drug is not approved for this indication. For some time, Selegelin was also administered to Alzheimer’s patients. However, meta-analyses showed that symptoms did not improve when taking selegelin.
Risks and side effects
Common side effects of selegelin include dry mouth, dizziness, and sleep disturbances. Loss of appetite, confusion, and low blood pressure may also occur. In severe cases, people suffer from hallucinations and anxiety. Another possible side effect of Selegelin is cardiac arrhythmias. These are noticeable by a heartbeat that is too fast, a heart rate that is too slow, or heart stuttering. Selegelin may increase the effects and also the side effects of psychostimulants, certain nasal drops, antihypertensive agents, low blood pressure agents, sedatives, and ethanol. Linezolid, an antibiotic, has MAO-inhibitory side effects. These can also be enhanced by selegelin, resulting in excess dopamine. Excess dopamine can result in anxiety and schizophrenia. Taking selegelin and antidepressants at the same time is counterproductive. A combination of the drugs can cause hyperthermia, seizures, mental disorders, and cardiovascular problems. In the worst case, coma may result. In particular, selective serotonin reuptake inhibitors (SSRIs) and fluoxetine must not be taken together with Selegelin.Drugs that are degraded via monoaminooxidases remain longer in the blood when taken simultaneously with Selegelin. No adverse effects are expected with combined ingestion of selegelin and tyramine-containing foods, such as cheese or red wine. Due to MAO selectivity, enough monoamine oxidase A is still available for amino acid degradation.
