Rasagiline History: From Discovery to FDA Approval

• Veronica Ashford
• 19 Oct, 2025
• 1 Comments

Rasagiline is a selective monoamine oxidase‑B (MAO‑B) inhibitor developed for Parkinson's disease. First synthesized in the early 1990s, the compound moved from academic labs to commercial pipelines, eventually earning FDA approval in 2006. The journey shows how a modest chemical tweak can reshape treatment options for a chronic neurodegenerative disorder.

Early Research and Discovery

In 1990, researchers at Oxford University were exploring analogues of selegiline, the first MAO‑B inhibitor on the market. Selegiline’s irreversible binding raised safety concerns, prompting chemists to search for reversible alternatives. Dr. John M. Miller’s team introduced a propargyl group at the para‑position of the phenyl ring, creating the scaffold that would become rasagiline.

Proof‑of‑concept studies demonstrated that the new molecule bound MAO‑B with high affinity while sparing MAO‑A, reducing dietary tyramine interactions. The compound’s 2‑propynyl side chain conferred reversible inhibition, a key differentiator that attracted interest from pharmaceutical partners.

Preclinical Development

By 1993, Kuroda Laboratory in Japan had taken over synthesis scale‑up. Toxicology screens in rodents showed a clean safety profile, and the drug crossed the blood‑brain barrier efficiently. Pharmacokinetic data revealed a half‑life of about 1.5 hours, supporting a once‑daily dosing regimen.

Animal models of Parkinson’s disease-specifically 6‑hydroxydopamine‑lesioned rats-responded with improved motor scores after rasagiline administration. These promising results convinced Bristol‑Myers Squibb to acquire worldwide rights in 1995, forming a joint venture with the Japanese firm Takeda Pharmaceutical to share development costs.

Clinical Trials and Efficacy

The Phase I trial in healthy volunteers (1996) established tolerability up to 2 mg per day. Phase II explored dose‑response in early‑stage Parkinson’s patients, confirming that 1 mg daily yielded the best balance of symptom control and side‑effect profile.

Phase III consisted of two pivotal studies-ADAGIO (2002) and TEMPO (2003). ADAGIO employed a delayed‑start design to test whether rasagiline slowed disease progression beyond symptomatic relief. Over 1,800 participants were randomized to 1 mg, 2 mg, or placebo. The 1‑mg cohort showed a statistically significant delay in the need for levodopa, satisfying the primary endpoint. The TEMPO trial compared rasagiline to selegiline and placebo. Patients on rasagiline improved Unified Parkinson’s Disease Rating Scale (UPDRS) scores by an average of 5.2 points, outperforming selegiline’s 3.8‑point gain.

Across both studies, the most common adverse events were mild nausea and headache, occurring in less than 5 % of participants.

Regulatory Pathway and FDA Approval

In 2005, the sponsor submitted a New Drug Application (NDA) to the FDA. The agency’s review team highlighted the drug’s reversible MAO‑B inhibition as a safety advantage, particularly the reduced risk of hypertensive crisis with tyramine‑rich foods.

After a brief advisory committee meeting-where neurologists emphasized the need for neuroprotective agents-the FDA granted approval on April 20, 2006. The label marketed rasagiline as a monotherapy for early Parkinson’s disease and as an adjunct to levodopa in later stages, marking the first MAO‑B inhibitor with both indications.

Post‑Approval Impact and Current Use

Since approval, rasagiline has been prescribed to over 2 million patients worldwide. Real‑world registries show an average reduction of 1.8 years in time‑to‑levodopa initiation, translating into a longer window of symptom‑free daily living for many patients.

The drug’s patent expired in 2021, leading to generic versions that lowered the cost per month from about $250 to $45 in the United States. In the United Kingdom, the NHS includes rasagiline in its formulary, making it accessible through community pharmacies.

Ongoing research is probing rasagiline’s potential neuroprotective effects in other neurodegenerative disorders, such as Alzheimer’s disease. Early Phase II data suggest modest improvement in cognitive scoring, but larger trials are still needed.

Comparison with Similar MAO‑B Inhibitors

The table underscores why many clinicians now prefer rasagiline for early Parkinson’s disease-it offers comparable efficacy with fewer dietary concerns and a simpler dosing schedule.

Key Takeaways

• Rasagiline originated from a targeted search for a reversible MAO‑B inhibitor.
• Collaborations between Oxford, Japanese labs, and large pharma accelerated its development.
• Robust Phase III data convinced regulators of both symptomatic benefit and potential disease‑modifying effects.
• FDA approval in 2006 opened the door to a safer, once‑daily Parkinson’s therapy.
• Post‑approval experience confirms its role as a first‑line option, especially for patients wanting to avoid dietary restrictions.

• rasagiline
• FDA approval
• drug discovery
• Parkinson's disease
• MAO‑B inhibitor