Rasagiline Mesylate

AHFS Class: Monoamine Oxidase B Inhibitors (28:36.32)

VA Class: CN500
VA Class: CN602
Chemical Name: (R)-2,3-dihydro-N-2-propynyl-1H-inden-1-amine methanesulfonate
Molecular Formula: C₁₂H₁₃N•CH₄O₃S

View the associated Essentials monograph.

Introduction

Rasagiline, a propargylamine, is an irreversible monoamine oxidase-B (MAO-B) inhibitor.^{1 2 3 4 5}

Uses

Parkinsonian Syndrome

Rasagiline is used as initial monotherapy or as adjunctive therapy to levodopa for the symptomatic treatment of idiopathic parkinsonian syndrome.^{1 2}

Efficacy of rasagiline as initial monotherapy in the management of parkinsonian syndrome has been established in a randomized, double-blind, placebo-controlled study of up to 26 weeks’ duration in patients with early disease who were not receiving dopaminergic antiparkinsonian agents or had not received any antiparkinsonian drug therapy.^{1 2 5} In this study, patients were randomized to receive rasagiline (1 or 2 mg once daily) or placebo; patients were not permitted to use levodopa, dopamine agonists, selegiline, or amantadine but could receive stable dosages of an anticholinergic agent as needed.^{1 5 8} The primary efficacy measurement was the change from baseline in the total score (i.e., combined scores from part I [mentation], part II [activities of daily living], and part III [motor function]) of the Unified Parkinson’s Disease Rating Scale (UPDRS); a reduction in the total score represented an improvement in mentation, activities of daily living, and/or motor function.^{1 5} Treatment with rasagiline was associated with substantially smaller increases in the UPDRS score (i.e., less functional decline) compared with treatment with placebo; efficacy of rasagiline dosages of 1 or 2 mg daily was comparable.^{1 5 8}

Efficacy of rasagiline as an adjunct to levodopa in the management of parkinsonian syndrome has been established in 2 multicenter, randomized, double-blind, placebo-controlled studies in patients with more advanced disease who were receiving long-term levodopa therapy (mean duration: 8 years; range: 5 months–32 years) in combination with a decarboxylase inhibitor and were experiencing motor fluctuations (e.g., end-of-dose “wearing off”, sudden or random “off” phenomena).^{1 3 4} In the first study, patients were randomized to receive rasagiline (0.5 or 1 mg daily) or placebo for 26 weeks;^{1 2 4} in the second study, patients were randomized to receive rasagiline (1 mg daily), entacapone (200 mg with every levodopa dose), or placebo, for 18 weeks.^{1 2 3} Patients in both studies continued receiving levodopa (average dosage: 700–800 mg daily) and were permitted to receive stable dosages of other antiparkinsonian agents; dopamine agonists were used in approximately 65% of patients in both studies, and entacapone was used in 35% of patients in the first study.^{1 3 4} The primary efficacy measurement was the change from baseline in the mean number of total daily hours spent in the “off” state (period of poor functioning and mobility), as measured by 24-hour home diaries.^{1 2 3 4 8} In these studies, therapy with rasagiline (1 mg daily) or entacapone was more effective than placebo in decreasing total daily “off” time;^{1 3 8} therapy with a lower dosage of rasagiline (0.5 mg daily) also resulted in decreased “off” time, but to a lesser extent.^{1 4} Duration of “off” time was reduced by a mean of 1.2–1.9, 1.4, 1.2, or 0.4–0.9 hours in patients receiving rasagiline 1 mg, rasagiline 0.5 mg, entacapone, or placebo, respectively.^{1 3 4} In addition, compared with placebo, treatment with rasagiline or entacapone was associated with substantial improvements in the UPDRS activities of daily living (ADL) score during the “off” period and the UPDRS motor function score during the “on” period.^{1 3 4} During the first 6 weeks of therapy, reduction in levodopa dosage was permitted if adverse dopaminergic effects (e.g., dyskinesia, hallucinations) occurred or worsened.^{1 3 4} In these studies, levodopa dosage was reduced in 9–17 or 6–8% of patients receiving rasagiline or placebo, respectively; levodopa dosage was reduced on average by about 9–13% in patients receiving rasagiline or about 7–13% in those receiving placebo.¹

Dosage and Administration

Administration

Rasagiline mesylate is administered orally once daily without regard to meals.^{1 2}

Dosage

The recommended adult dosage of rasagiline as initial monotherapy for the management of parkinsonian syndrome is 1 mg once daily.¹

The recommended initial adult dosage of rasagiline as adjunctive therapy with levodopa for the management of parkinsonian syndrome is 0.5 mg once daily.¹ If an adequate response is not achieved, dosage may be increased to 1 mg once daily.¹ During adjunctive therapy with levodopa, reduction in levodopa dosage may be considered if adverse dopaminergic effects (e.g., dyskinesia, hallucinations) occur.¹ In clinical studies, approximately 9–17% of patients receiving 0.5 or 1 mg of rasagiline daily required a reduction in levodopa dosage; the average reduction in the daily levodopa dosage was about 9–13%.¹ (See Uses: Parkinsonian Syndrome.)

Concomitant use of rasagiline with ciprofloxacin or other cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors has been shown, or would be expected, to increase plasma rasagiline concentrations by up to twofold.¹ Therefore, when used concomitantly with ciprofloxacin or other CYP1A2 inhibitors,^{1 2 8} the manufacturer of rasagiline states that rasagiline dosage should be limited to 0.5 mg once daily.¹

Special Populations

Patients with mild (Child-Pugh score of 5–6) hepatic impairment should receive a rasagiline dosage of 0.5 mg once daily; rasagiline should not be used in patients with moderate or severe (Child-Pugh score of 7 or greater) hepatic impairment.^{1 2} (See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

No dosage adjustment is necessary in patients with mild renal impairment or in geriatric patients.¹

Cautions

Contraindications

Concomitant use with cyclobenzaprine, dextromethorphan, meperidine, mirtazapine, methadone, propoxyphene, tramadol, St. John’s wort (Hypericum perforatum), sympathomimetic amines (e.g., amphetamines, ephedrine, phenylephrine, phenylpropanolamine [no longer commercially available in the US], pseudoephedrine), or other monoamine oxidase (MAO) inhibitors.¹ (See Drug Interactions.)

Elective surgery that requires general anesthetics, cocaine, or local anesthetics containing sympathomimetic vasoconstrictors.¹ Rasagiline should be discontinued at least 14 days prior to elective surgery; if surgery is needed sooner (i.e., less than 14 days after discontinuance of rasagiline), benzodiazepines, mivacurium, rapacuronium, fentanyl, morphine, or codeine may be used with caution.^{1 8}

Pheochromocytoma.¹

Warnings/Precautions

Warnings

Hypertensive Crisis. Hypertensive crisis (i.e., cheese reaction), manifested as marked elevations in systemic blood pressure, may occur at any dose of rasagiline following ingestion of foods containing large amounts of tyramine or drug preparations containing sympathomimetic amines. (See Description.)¹ Hypertensive crisis may be fatal and requires immediate treatment or hospitalization.¹

Patients should be advised to avoid foods containing large amounts of tyramine and drug preparations containing sympathomimetic amines during and for 2 weeks following discontinuance of rasagiline.^{1 8} (For additional information on foods and beverages with high tyramine contents or drug preparations containing sympathomimetic amines, see Drug Interactions: Food and Drugs Associated with Hypertensive Crisis in the Monoamine Oxidase Inhibitors General Statement 28:16.04.12.) Patients also should be instructed on how to recognize manifestations of a hypertensive crisis and to immediately notify a clinician if such manifestations occur.¹ (See Advice to Patients.)

Concomitant Use with Antidepressant Agents. Concomitant use of selective (i.e., selegiline) or nonselective (e.g., phenelzine, tranylcypromine) MAO inhibitors with selective serotonin-reuptake inhibitors (SSRIs), selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), or tricyclic antidepressants has resulted in severe, sometimes fatal, adverse effects.¹ Therefore, concomitant use of rasagiline with these antidepressant agents generally should be avoided.¹ (See Drug Interactions: Antidepressant Agents.)

Concomitant Use with Ciprofloxacin or Other CYP1A2 Inhibitors. Concomitant use of rasagiline with ciprofloxacin or other cytochrome P-450 (CYP) isoenzyme 1A2 inhibitors has been shown, or would be expected, to increase plasma rasagiline concentrations by up to twofold.¹ Adjustment of rasagiline dosage is recommended.^{1 8} (See Dosage and Administration: Dosage and also see Drug Interactions: Drugs Affecting Hepatic Microsomal Enzymes.)

Major Toxicities

Orthostatic Hypotension. Orthostatic hypotension was reported in approximately 3% of patients receiving rasagiline as monotherapy.¹ When used as adjunctive therapy with levodopa, orthostatic hypotension was reported in 6–9% of patients and resulted in discontinuance of the drug in less than 1% of patients.¹ Data from clinical studies indicate that orthostatic hypotension occurs most frequently during the first 2 months of rasagiline therapy and less frequently over time.¹

Hallucinations. Hallucinations were reported in approximately 1 or 4–5% of patients receiving rasagiline as monotherapy or as adjunctive therapy with levodopa, respectively, and resulted in discontinuance of the drug in approximately 1% of patients.¹

Patients should be cautioned of the possibility of developing hallucinations and instructed to notify a clinician should these manifestations occur.¹

General Precautions

Melanoma. Data from epidemiologic studies indicate that patients with Parkinson’s disease have an approximately twofold to fourfold greater risk of developing melanoma than the general population; however, it is unclear whether the observed increased risk is related to the underlying disease or to antiparkinsonian drug therapy.¹ The risk of developing melanoma^{4 5} in patients receiving rasagiline appears to be greater than that in the general population but comparable to that in patients with Parkinson’s disease.¹

Because of these findings, patients and clinicians should monitor for melanomas frequently.¹ The manufacturer recommends that dermatologic examinations be performed by qualified clinicians (e.g., dermatologists) periodically;¹ the frequency of dermatologic examinations should be determined by the patient’s dermatologist.⁸

Specific Populations

Pregnancy. Category C.¹ (See Users Guide.)

Lactation. Inhibits prolactin secretion in rats; may inhibit milk secretion in women.^{1 8} Not known whether rasagiline is distributed into milk; caution is advised if the drug is administered in nursing women.¹

Pediatric Use. Safety and efficacy of rasagiline have not been established in pediatric patients younger than 18 years of age.^{1 8}

Geriatric Use. Approximately half of patients in clinical studies were 65 years of age or older.¹ No overall differences in safety relative to younger adults were observed.¹

Hepatic Impairment. Following daily administration for 7 days, the area under the plasma concentration-time curve (AUC) or peak plasma concentration of rasagiline was increased by 2- or 1.4-fold, respectively, in patients with mild (Child-Pugh score of 5–6) hepatic impairment and by seven- or twofold, respectively, in patients with moderate (Child-Pugh score of 7–9) hepatic impairment.¹

Dosage adjustment is recommended in patients with mild hepatic impairment.¹ Use is not recommended in patients with moderate or severe (Child-Pugh score of 7 or greater) hepatic impairment.^{1 2} (See Dosage and Administration: Special Populations.)

Renal Impairment. Conclusive data on the pharmacokinetics of rasagiline in patients with renal impairment are not available.^{1 8} However, because unconjugated rasagiline is not excreted by the kidneys, no dosage adjustment is necessary in patients with mild renal impairment.¹

Common Adverse Effects

Adverse effects reported in 5% or more of patients receiving rasagiline as initial monotherapy and occurring more frequently than placebo include flu syndrome,¹ arthralgia,^{1 5} depression,¹ dyspepsia,¹ fall,¹ headache,^{1 5} conjunctivitis,¹ fever,¹ gastroenteritis,¹ rhinitis,¹ arthritis,¹ ecchymosis,¹ malaise,¹ neck pain,¹ paresthesia,¹ and vertigo.^{1 8}

Adverse effects reported in 5% or more of patients receiving rasagiline as adjunctive therapy with levodopa and occurring more frequently than placebo include dyskinesia,^{1 3 4} accidental injury,¹ weight loss,^{1 4} orthostatic hypotension,^{1 3} vomiting,^{1 3 4} anorexia,^{1 4} arthralgia,¹ abdominal pain,¹ nausea,^{1 3} constipation,^{1 3} dry mouth,^{1 3} rash,¹ ecchymosis,¹ somnolence,^{1 3} paresthesia,¹ headache, ¹ fall,¹ diarrhea,^{1 3} dyspepsia,¹ abnormal dreams,^{1 3} hallucinations,^{1 3} ataxia,¹ dyspnea,¹ infection,¹ neck pain,¹ sweating,¹ tenosynovitis,¹ dystonia,¹ gingivitis,¹ hemorrhage,¹ hernia, and myasthenia.^{1 8}

Drug Interactions

Rasagiline is extensively metabolized, mainly via hepatic cytochrome P-450 (CYP) 1A2 isoenzyme.^{1 2} The drug does not inhibit CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A in vitro.^{1 2}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP1A2: Pharmacokinetic interaction observed during concomitant use with ciprofloxacin (increased plasma rasagiline concentrations).^{1 2} Dosage of rasagiline should be limited to 0.5 mg once daily in patients receiving the drug concomitantly with ciprofloxacin or other CYP1A2 inhibitors.^{1 8}

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP1A2: Pharmacokinetic interaction with theophylline or other substrates of CYP1A2 unlikely.^{1 2}

Substrates of 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A: Pharmacokinetic interaction unlikely.^{1 2}

Antidepressant Agents

Selective Serotonin-reuptake Inhibitors (SSRIs)

Potential pharmacologic interaction resembling serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability with rapid vital sign fluctuations, and mental status changes that may progress to extreme agitation, delirium, coma, and death).^{1 2} Concomitant use generally should be avoided.¹ At least 14 days should elapse between discontinuance of rasagiline and initiation of an SSRI.¹ Because both fluoxetine and its principal metabolite have relatively long half-lives, the manufacturer of rasagiline recommends that at least 5 weeks (or longer with high-dose or long-term fluoxetine therapy) elapse between discontinuance of fluoxetine therapy and initiation of rasagiline.¹

Selective Serotonin- and Norepinephrine-reuptake Inhibitors (SNRIs)

Potential pharmacologic interaction (hyperthermia, rigidity, myoclonus, autonomic instability with rapid vital sign fluctuations, and mental status changes progressing to extreme agitation, delirium, coma, and death).¹ Concomitant use generally should be avoided.¹ At least 14 days should elapse between discontinuance of rasagiline and initiation of an SNRI.¹

Tetracyclic Antidepressants

Concomitant use with mirtazapine is contraindicated.¹ (See Cautions: Contraindications.)

Tricyclic Antidepressants

Potential pharmacologic interaction resembling serotonin syndrome (behavioral and mental status changes, hyperpyrexia, diaphoresis, muscular rigidity, hypertension, syncope, and death).^{1 8} Concomitant use generally should be avoided.¹ At least 14 days should elapse between discontinuance of rasagiline and initiation of tricyclic antidepressants.¹

Cyclobenzaprine

Concomitant use is contraindicated.¹ (See Cautions: Contraindications.)

Dextromethorphan

Potential pharmacologic interaction (brief episodes of psychosis or bizarre behavior).¹ Concomitant use is contraindicated.¹ (See Cautions: Contraindications.)

Levodopa

Potential pharmacologic (increased adverse dopaminergic effects, increased risk of dyskinesia and orthostatic hypotension) and pharmacokinetic interaction (modest increase in plasma rasagiline concentrations).^{1 2} Reduction in levodopa dosage may be considered; adjustment of rasagiline dosage is not necessary.¹ (See Dosage and Administration: Dosage.)

Monoamine Oxidase (MAO) Inhibitors

Potential pharmacokinetic interaction (increased risk of nonselective MAO inhibition, possibly resulting in a hypertensive crisis).¹ Concomitant use is contraindicated.¹ (See Cautions: Contraindications.) At least 14 days should elapse between discontinuance of rasagiline and initiation of other MAO inhibitors.¹

Opiate Agonists

Potential pharmacologic interaction (resembling serotonin syndrome) with meperidine (coma, severe hypertension or hypotension, severe respiratory depression, seizures, malignant hyperpyrexia, excitation, peripheral vascular collapse, and death).^{1 2} Concomitant use with meperidine, methadone, propoxyphene, or tramadol is contraindicated.^{1 2} (See Cautions: Contraindications.) At least 14 days should elapse between discontinuance of rasagiline and initiation of meperidine.¹

St. John’s wort (Hypericum perforatum)

Concomitant use is contraindicated.¹ (See Cautions: Contraindications.)

Sympathomimetic Amines

Potential pharmacologic interaction (severe hypertensive reaction or hypertensive crisis).¹ (See Hypertensive Crisis under Warnings/Precautions: Warnings, in Cautions.) Concomitant use with amphetamines, ephedrine, phenylephrine, phenylpropanolamine (no longer commercially available in the US), or pseudoephedrine is contraindicated during and for 2 weeks following discontinuance of rasagiline.^{1 8} (See Cautions: Contraindications.)

Tyramine-rich Foods, Beverages, or Dietary Supplements

Potential pharmacologic interaction (severe hypertensive reaction or hypertensive crisis).¹ (See Hypertensive Crisis under Warnings/Precautions: Warnings, in Cautions.) Foods, beverages, and dietary supplements containing large amounts of tyramine (e.g., aged/fermented meat or cheese, pickled herring, pods of fava beans, sauerkraut, soy sauce, tofu, concentrated yeast extract, red wine, tap/draft beer) should be avoided during and for 2 weeks following discontinuance of rasagiline.¹

Description

Rasagiline mesylate, a propargylamine, is an irreversible monoamine oxidase-B (MAO-B) inhibitor.^{1 2 3 4 5} MAO is a mitochondrial enzyme that regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues.¹ There appear to be at least 2 isoforms of MAO, MAO-A and MAO-B, which differ in localization and substrate specificity.² MAO-A, predominantly found in the GI tract and liver, regulates the metabolic degradation of circulating catecholamines and dietary amines (e.g., tyramine).^{1 2} MAO-B, predominantly found in the brain, regulates the metabolic degradation of dopamine and phenylethylamine.^{1 2} Inhibition of MAO-A in the periphery results in systemic absorption of dietary amines (e.g., tyramine), which, in substantial amounts, can cause release of norepinephrine and subsequent substantial increases in blood pressure.^{1 2} (See Hypertensive Crisis under Warnings/Precautions: Warnings, in Cautions.) Inhibition of MAO-B results in increased extracellular concentrations of dopamine and, therefore, enhanced dopaminergic activity in the striatum.^{1 2 3} While the precise mechanisms of activity of rasagiline have not been fully characterized, data from ex vivo animal studies indicate that the drug potently and irreversibly inhibits MAO-B in brain, liver, and intestinal tissues;^{1 6} the selectivity of rasagiline in inhibiting MAO-B (and not MAO-A) in humans has not been fully elucidated to avoid restriction of dietary tyramine and sympathomimetic amines.¹

Rasagiline is rapidly absorbed; following oral administration, peak plasma concentrations are achieved in approximately 1 hour.^{1 2} The absolute bioavailability of rasagiline is about 36%.^{1 2} Following administration with a high-fat meal, peak plasma rasagiline concentrations and area under the plasma concentration-time curve (AUC) decreased by approximately 60 and 20%, respectively; because AUC is not substantially affected, rasagiline may be administered with or without food.^{1 2} Rasagiline readily crosses the blood-brain barrier.^{2 8} The mean steady-state or terminal half-life of rasagiline is 3¹ or 1.34² hours, respectively; however, there is no correlation between rasagiline’s pharmacokinetic profile and its pharmacologic effects because the drug irreversibly inhibits MAO-B, and restoration of normal enzyme activity depends on the rate of de novo enzyme synthesis.^{1 2} Rasagiline is approximately 88–94% bound to plasma proteins, with 61–63% bound to albumin.¹

Rasagiline undergoes almost complete biotransformation in the liver prior to excretion.¹ The drug is metabolized via dealkylation and/or hydroxylation by the cytochrome P-450 (CYP) microsomal enzyme system, principally by isoenzyme 1A2.^{1 2} Approximately 62 and 7% of an oral dose of rasagiline is excreted in urine and feces, respectively, as metabolites over 7 days; less than 1% of the drug is excreted as unchanged drug in urine.^{1 2}

Advice to Patients

Importance of recognizing the tyramine content of foods, beverages, and dietary supplements, and avoiding those containing large amounts of tyramine (e.g., aged/fermented meat or cheese, pickled herring, pods of fava beans, sauerkraut, soy sauce, tofu, concentrated yeast extract, red wine, tap/draft beer) during and for 2 weeks following discontinuance of rasagiline.¹

Importance of avoiding nonprescription (over-the-counter) preparations containing sympathomimetic amines (e.g., ephedrine, phenylephrine, phenylpropanolamine [no longer commercially available in the US], pseudoephedrine) during and for 2 weeks following discontinuance of rasagiline.¹

Importance of recognizing manifestations of a hypertensive crisis (e.g., severe headache, blurred vision or visual disturbances, difficulty thinking, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, manifestations of a stroke) and promptly seeking medical attention if such manifestations occur.¹

Importance of informing clinicians promptly if hallucinations occur.¹

Risk of increased dyskinesia and orthostatic hypotension when used concomitantly with levodopa.¹

Importance of monitoring for melanomas frequently and receiving dermatologic examinations (i.e., performed by dermatologists) periodically.¹

Importance of taking rasagiline as prescribed.¹ If a dose is missed, omit the dose and administer the next dose at the regularly scheduled time on the following day.¹

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and/or herbal products (e.g., St. John’s wort), as well as any concomitant illnesses.¹

Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer’s labeling should be consulted. It is essential that the manufacturer’s labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Rasagiline Mesylate

Routes	Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	0.5 mg (of rasagiline)	Azilect®	Teva Neuroscience
		1 mg (of rasagiline)	Azilect®	Teva Neuroscience

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit www.drugstore.com.

Azilect 0.5MG Tablets (TEVA NEUROSCIENCE): 30/$271.12 or 90/$730.4

Azilect 1MG Tablets (TEVA NEUROSCIENCE): 30/$250 or 90/$736.16

Selected Revisions October 2007, © Copyright, December 2006, American Society of Health-System Pharmacists, Inc. 7272 Wisconsin Avenue, Bethesda, MD 20814.

References

1. Teva Neuroscience, Inc. Azilect^® (rasagiline mesylate) tablets prescribing information. Teva Neuroscience, Inc. Kansas City, MO; 2006 May.

2. Chen JJ and Swope DM. Clinical pharmacology of rasagiline: A novel, second-generation propargylamine for the treatment of Parkinson disease. J Clin Pharmacol. 2005; 45:878-94.

3. Rascol O, Brooks DJ, Melamed E et al for the LARGO study group. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): A randomised, double-blind, parallel-group trial. Lancet. 2005; 365:947-54.

4. Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: The PRESTO Study. Arch Neurol. 2005; 62:241-8.

5. Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: The TEMPO Study. Arch Neurol. 2002; 59:1937-43.

6. Youdim MBH, Gross A, and Finberg JPM. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol. 2001; 132:500-6.

8. Teva Neuroscience, Inc., Overland Park, KS: Personal communication.