MAO-B inhibitors in the treatment of Parkinson's Disease
Monoamine Oxidase B Inhibitors, such as Selegiline and Rasagiline, are commonly used by patients with PD because of their potential disease modifying and neuroprotective effects . This drug class is considered a potential disease modifier due to its ability to inhibit the monoamine oxidase type B (MAO-B) enzyme, which naturally breaks down dopamine in the brain.By inhibiting the breakdown of the MAO-B enzyme, these drugs are able to extend the effects of dopamine at the CNS synapse ). However, more research needs to be done on the ability of MAO-B inhibitors to slow the progression of PD. MAO-B inhibitors exhibit neuroprotection by decreasing dopamine oxidation, therefore preventing excessive production of free radicals, while prolonging the effects of endogenous dopamine ). MAO-B inhibitors can be used as an initial drug in the treatment of Parkinson’s Disease or can be combined with Levodopa in order to reduce motor fluctuations.
The prototypical selective, irreversible MAO-B inhibitor, Selegiline, is absorbed in the GI tract and then distributed to tissues throughout the body, including the brain. Selegiline is metabolized to L-amphetamine-like metabolites which may promote insomnia . This drug is primarily metabolized in the liver and then excreted by the kidneys . Selegiline has an oral bioavailability of 10% and an oral clearance rate of 59 L/min . This drug is given at a therapeutic dose of 10mg/day and has a half-life of 10 hours. Selegiline is typically administered twice per day as a 5mg oral tablet . If this dose is increased Selegiline will lose it’s selective ability.
Rasagiline, another selective, irreversible MAO-B inhibitor, is metabolized into aminoindan in the liver by cytochrome p450 type 1A2, which means it does not have the amphetamine-like effects that Selegiline displays and may be preferred . Its oral bioavailability is 35% and it reaches its therapeutic maximum after 0.5-1 hour . The oral clearance rate of Rasagiline is 94.3 L/day. This drug is given at a recommended dose of 0.5-1 mg/day and has a half-life or 1.5-3.5 hours . It is typically administered once per day as a 0.5mg or 1mg oral tablet .
When used in adjunct with Levodopa both Selegiline and Rasagiline have been known to decrease motor fluctuations in patients with PD . These two drugs are relatively safe compared to other MAO inhibitors due to their selective ability . Common adverse effects of other MAO-B Inhibitors may include dizziness, headache, GI distress, and sedation .
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