What is Rasagiline?
Rasagiline (1H-Inden-1-amine, 2, 3-dihydro-N-2-propynyl-, (1R)-, methanesulfonate, also known as rasagiline mesylate, AGN 1135, and TVP-1012) is a second-generation irreversible monoamine oxidase inhibitor (MAOI). It is derived from the propargylamine class of compounds (see selegiline) and was developed by Teva Pharmaceuticals, which sells it under the brand name Azilect. As it is a relatively new drug, there is no generic equivalent available.
How does it work?
Rasagiline was developed as an alternative to selegiline. Selegiline is widely prescribed for Parkinson’s disease and has structural similarities to amphetamines. The idea was that rasagiline would have the benefits of selegiline without the possibility of cardiac and psychiatric side effects. It is more specific for the B isoform of MAO, but it can bind to and inhibit the A isoform at very high concentrations. While this mechanism does play into the reason for rasagiline’s efficacy, it also is protective against neurotoxic insults. This is believed to be due to its ability to stabilize mitochondrial membrane potential. Rasagiline and other propargylamines can prevent mitochondria from becoming “leaky”, likely protecting neurons from neurotoxins and oxidative stress.
Long-term rasagiline regimens also increase antioxidants, such as superoxide dismutase and catalase in the central nervous system (CNS). It may also increase concentrations of glial cell-derived neurotrophic factor, nerve growth factor, and brain-derived neurotrophic growth factor. All of these proteins protect neurons and, as their names imply, facilitate their growth and survival.
The primary indication for rasagiline is as a treatment for Parkinson’s disease, it has been shown to protect dopaminergic neurons in the substantia nigra from neuronal death. It is also under investigation for treating Alzheimer’s disease patients; preliminary studies have indicated that it may also protect non-dopaminergic neurons. Research in a mouse model suggests that it may prevent the death of photoreceptors in the retina.
In addition to its uses in patient populations, it may improve mood, motivation, and age-related cognitive decline in healthy people. In Parkinson’s disease patients without cognitive dysfunction, rasagiline improved cognitive test scores that assessed verbal fluency, semantic fluency, and attention. However, no large-scale studies have been done in healthy populations, and the drug is still patented, so it quite expensive (see below).
Rasagiline Side Effects
Side effects are generally minimal when rasagiline is taken within the appropriate therapeutic dose range. The most common were postural hypotension (sudden fall in blood pressure upon rising from a seated or lying position), headache, and upset stomach. Gastrointestinal problems may be avoided by taking rasagiline with food.
Rasagiline comes in tablet form and is usually taken once a day (with or without food). It should be taken at the same time every day. Individuals that also take levodopa (L-DOPA) are usually started on a dose of 0.5 mg/day, which may be increased to 1.0 mg/day. There is no generic form, and this drug is very expensive. Thirty 0.5 mg tablets are $360.00, but there seems to be a discount: the same amount of 1 mg tablets are $346.00.
Because rasagiline is heavily metabolized by the liver, it should not be taken by people with serious liver problems. Individuals should ask their pharmacist if any of their prescriptions utilize the CYP1A2 isoform, because taking rasagiline in addition may overload the liver enzyme’s ability to metabolize the compounds. The pharmacist would likely recommend a low dose (0.5 mg/day).
Like other MAOIs, foods rich in tyramine (such as cheese) may interfere with drug metabolization. However, this does not appear to be a problem in healthy volunteers taking an appropriate dose, and all rasagiline clinical trials have been good results. Dosages above 2 mg per day are not advised, because rasagiline loses its specificity for MAOB and also inhibits MAOA, which is the isoform responsible for tyramine breakdown. Rasagiline should not be taken in conjunction with other MAOIs.
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Gulyás, Balázs, Elena Pavlova, Péter Kása, Károly Gulya, Lidia Bakota, Szilvia Várszegi, Éva Keller, Mónika Csilla Horváth, Sangram Nag, and István Hermecz. “Activated MAO-B in the Brain of Alzheimer Patients, Demonstrated by [11C]-l-deprenyl Using Whole Hemisphere Autoradiography.” Neurochemistry International 58.1 (2010): 60-68. Print.
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