There are a few important differences between rasagiline vs selegiline. Both drugs were originally developed by Teva Neuroscience in Israel, but rasagiline is much newer. Rasagiline is the successor of selegelline.
Our Verdict on Rasagiline Verses Selegiline
Rasagiline does seem to be an improvement on selegeline. It’s more potent, so lower doses can be used, and it lacks amphetamine metabolites. There’s also more evidence that rasagiline is neuroprotective. This means that it might be a disease-modifying treatment for Parksinon’s disease, but more research is needed.
Key differences between selegiline vs rasagiline include:
- Indications. Selegiline is indicated for the treatment of Parkinson’s disease, palliative treatment of Alzheimer’s disease, and for depression at high doses. Rasagiline is approved for the treatment of idiopathic Parkinson’s disease, as monotherapy and as an adjunct to levodopa.
- Metabolites. l-methamphetamine and amphetamine are metabolites of selegiline. Rasagiline is metabolized to the non-amphetamine 1-(R)-aminoindan.
- Potency. Rasagiline is about five times as potent as selegiline. Thus, lower doses can be used.
- Side effects. Selegiline is more likely to cause insomnia, hypertension and other side effects associated with increased catecholamines (dopamine, norepinephrine). Rasagiline is probably better tolerated.
- Neuroprotection. Both selegiline and rasagiline have demonstrated neuroprotective effects in vitro and in animal models. It remains unclear whether these drugs have neuroprotective/disease-modifying effects in actual Parkinson’s patients. Rasagiline is thought to possess more robust neuroprotective effects1.
Rasagiline/selegeline irreversibly and selectively inhibit an enzyme called monoamine oxidase B (MAO-B). In high doses, they inhibit MAO-A too, but this effect is not clinically significant at prescribed dosages. MAO-A and B are subtypes of enzyme that metabolizes dopamine. By inhibiting dopamine metabolism, selegiline/rasagiline increase synaptic dopamine levels.
Selegiline and rasagiline are used for the treatment of Parkinson’s disease. Since dopamine function is impaired in both Parkinson’s disease and ADHD, MAO-B inhibitors effectively treat these conditions. When either drug is administered with levodopa (a precursor to dopamine), they enhance its action. A substantially lower dose of levodopa is effective when it is co-administered with selegiline/rasagiline.
|Dosage||0.5 – 1mg (oral)||5mg (oral); 6-12mg (patch)|
|Biological half-life||3 hours||10 hours (oral); 18-25 hours (transdermal)|
|Broken down via||CYP1A2||CYP2D6, CYP2C19, others|
Amphetamine Metabolites of Selegiline
When comparing selegiline vs rasagiline, note that selegiline has (meth)amphetamine metabolites whereas rasagiline does not. The ratio of l-methamphetamine to amphetamine metabolites for selegiline is estimated to be 2.8.
Some individuals may be concerned about amphetamine neurotoxicity related to selegiline use. Rasagiline was developed as a successor to selegiline precisely for this reason: its lack of amphetamine metabolites. The major metabolite of rasagiline is 1-(R)-aminoindan, a non-amphetamine that inhibits both MAO-A and B reversibly and with less potency.
The rational for the development of rasagiline was to create a “cleaner” version of selegiline.
But if prescribed off-label for the treatment of ADHD, selegeline may actually be preferred because of its amphetamine metabolites. Both amphetamine and levomethamphetamine enhance concentration and treat the inattentive symptoms of ADHD.
Selegiline/rasagiline were originally thought to be “disease-modifying” drugs in the treatment of Parkinson’s disease. The expectation was that this class of medications would protect dopaminergic neurons from oxidative stress by multiple mechanisms. One such mechanism was decreased hydrogen peroxide (H2O2), which is naturally produced by MAO-B’s metabolism of dopamine.
It remains unclear whether these drugs are disease-modifying. The FDA has repeatedly rejected TEVA pharmaceuticals request for an on-label indication of neuroprotection in Parkinson’s disease.
It remains undisputed that selegiline/rasagiline relieve symptoms of Parkinson’s, when combined with levodopa. They’re also appropriate as monotherapy for newly diagnosed Parkinson’s disease.
There’s a lot of in vitro and animal model evidence of neuroprotection. But if selegiline/rasagiline were truly neuroprotective, we would expect that these drugs slow the progression of Parkinson’s. There is some tentative evidence that rasagiline slows disease progression, but more studies are needed to reach definitive conclusions.
Selegiline [seh-LEDGE-ah-leen], also called deprenyl [DE-pre-nill], selectively inhibits MAO Type B (which metabolizes dopamine) at low to moderate doses but does not inhibit MAO Type A (which metabolizes norepinephrine and serotonin) unless given at above recommended doses, where it loses its selectivity. By thus decreasing the metabolism of dopamine, selegiline has been found to increase dopamine levels in the brain (Figure 8.10). Therefore, it enhances the actions of levodopa when these drugs are administered together. Selegiline substantially reduces the required dose of levodopa. Unlike nonselective MAO inhibitors, selegiline at recommended doses has little potential for causing hypertensive crises. However, if selegiline is administered at high doses, the selectivity of the drug is lost, and the patient is at risk for severe hypertension. [Note: Early reports of possible neuroprotective effects of selegiline have not been supported by long-term studies.] Selegiline is metabolized to methamphetamine and amphetamine, whose stimulating properties may produce insomnia if the drug is administered later than midafternoon. (See p. 148 for the use of selegiline in treating depression). Rasagiline [ra-SA-gi-leen], an irreversible and selective inhibitor of brain (MAO) Type B, has five times the potency of selegiline. Unlike selegiline, it is not metabolized to an amphetamine-like substance.
Naoi M, Maruyama W, Youdim MB, Yu P, Boulton AA. Anti-apoptotic function of propargylamine inhibitors of type-B monoamine oxidase. Inflammopharmacology. 2003;11(2):175-81. ↩