Epistemis

Rasagiline

  • Selective and Irreversible MAO-B Inhibitor

Irreversible second-generation MAO-B inhibitor, with a clinical potency greater than selegiline and free of stimulant amphetamine metabolites.

Mechanism

Chemical and Commercial Profile

Common trade names: Azilect, Rasagilina Normon.
Group: Antiparkinsonian, selective irreversible inhibitor of the enzyme monoamine oxidase type B.

Mechanism of Action

Rasagiline acts by blocking the specific, irreversible, high-affinity enzyme monoamine oxidase type B (MAO-B), located in the glia cells and astrocytes of the striatum. By covalently binding to the flavin group of the active center of the enzyme, it prevents the oxidative degradation of extracellular dopamine in the striatum, prolonging its permanence and stimulation of striatal dopamine receptors. It has 100 times greater binding selectivity for MAO-B compared to MAO-A.

Pharmacokinetics

Pharmacokinetics

  • Absorption: Rapid and complete after oral intake; bioavailability of 35% due to an important hepatic first-pass metabolism. The plasma peak is reached at the time of intake.
  • Distribution: Very high binding to plasma proteins (90%). Distribution volume of 1.4 L/kg. It easily crosses the blood-brain barrier.
  • Metabolism: Hepatic oxidative catalyzed mainly by the isoenzyme CYP1A2. It generates the main active metabolite 1-aminoindane (which lacks amphetamine-type stimulant effects and presents intrinsic neuroprotective properties in preclinical models).
  • Excretion: Renal (60%) mainly in the form of inactive conjugated metabolites and 20% in unchanged form.
  • Half-life (t1/2): Short plasma 3 hours; however, **biological half-life is weeks** due to irreversible enzymatic inhibition. The clinical effect lasts until the MAO-B enzyme is synthesized *de novo* by glial cells (which requires 10 to 14 days).

Indicators and dose

Indications

  • Treatment of Idiopathic Parkinson's Disease as initial monotherapy (to delay the need for levodopa, with controversial evidence of delay in disease progression - ADAGIO study), or in adjuvant combination to reduce motor fluctuations.

Dosage and Settings

  • Dose of choice: 1 mg once daily orally (with or without food). It does not require a progressive titration phase.
  • Liver Failure: Decrease the daily dose to 0.5 mg/day in compensated Child-Pugh A cirrhosis; absolutely contraindicated in Child-Pugh B or C by the hepatic CYP1A2-dependent elimination pathway.
  • Renal Failure: It does not require special dose adjustments, but caution is recommended in hemodialysis due to low renal elimination.

Security

Contraindications

  • Concomitant use with other monoamine oxidase inhibitors (MAOIs) or with **pethidine, tramadol or methadone** (risk of severe serotonin syndrome and hyperthermia).
  • Severe decompensated liver failure (Child-Pugh C).

Adverse Effects (ADR)

Safety Alert · Serotonin Syndrome

The concurrent use of rasagiline with selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants presents a potential risk of triggering severe serotonin syndrome and malignant hyperthermia due to excess central serotonin. Although the risk is low at selective doses, close monitoring is recommended if they are associated in a clinically essential way.

  • CNS: Diffuse headache, dizziness, visual hallucinations (especially in the elderly), persecutory delusions, impulse control disorder (compulsive gambling, hypersexuality), nocturnal nightmares, drowsiness.
  • Gastrointestinal: Temporary nausea, moderate stomach pain of early onset.
  • Dermatological: Mild maculopapular rash (1-2%). Rare cases of worsening of premalignant skin lesions (melanoma).

Clinical Interactions

  • CYP1A2 inhibitors: Fluvoxamine, ciprofloxacin, and estrogens double the serum concentration of rasagiline, requiring a dose reduction by half (0.5 mg/day).
  • Sympathomimetics: Nasal decongestants such as pseudoephedrine or phenylephrine can trigger fatal hypertensive emergencies due to adrenergic synergy if selectivity is lost at high doses.

Pregnancy and Breastfeeding

FDA Category: C. Very limited human data; associates decreased embryonic growth in animals. Breastfeeding: Absolutely contraindicated. Like other dopaminergic drugs, it potently inhibits pituitary prolactin release reflexively, suppressing lactation, in addition to being excreted in breast milk.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousEntacapone / Tolcapone
System
Antiepileptics and Antiparkinsonians
Cluster
Selective and Irreversible MAO-B Inhibitor
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