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 Parkinson's Disease because of their potential disease modifying and neuroprotective effects [1]. 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[1].By inhibiting the breakdown of the MAO-B enzyme, these drugs are able to extend the effects of dopamine at the CNS synapse [2][3]. 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 [4][5]. 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[1].

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[6]. Selegiline is metabolized to L-amphetamine-like metabolites which may promote insomnia [1]. This drug is primarily metabolized in the liver and then excreted by the kidneys [6]. Selegiline has an oral bioavailability of 10% and an oral clearance rate of 59 L/min [7]. This drug is given at a therapeutic dose of 10mg/day and has a half-life of 10 hours[1]. Selegiline is typically administered twice per day as a 5mg oral tablet [8]. If this dose is increased Selegiline will lose it’s selective ability[1].

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 [9]. Its oral bioavailability is 35% and it reaches its therapeutic maximum after 0.5-1 hour [9]. The oral clearance rate of Rasagiline is 94.3 L/day[9]. 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 [9]. It is typically administered once per day as a 0.5mg or 1mg oral tablet [8].

When used in adjunct with Levodopa both Selegiline and Rasagiline have been known to decrease motor fluctuations in patients with PD [1]. These two drugs are relatively safe compared to other MAO inhibitors due to their selective ability [10]. Common adverse effects of other MAO-B Inhibitors may include dizziness, headache, GI distress, and sedation [10].    


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