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MyDeficiencies

Rasagiline

selective MAO-B inhibitor (irreversible, propargylamine)

Also sold as Azilect.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Rasagiline carries essentially no classical depletion machinery. Per the AZILECT and generic rasagiline FDA/DailyMed labeling, rasagiline undergoes almost complete hepatic biotransformation by N-dealkylation and/or hydroxylation, with CYP1A2 "the major isoenzyme involved in rasagiline metabolism," before glucuronide conjugation and renal/fecal elimination (62% of dose recovered in urine and 7% in feces over 7 days, less than 1% as unchanged drug); the label states rasagiline "is unlikely to cause any clinically significant interference" with CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A substrates, describes no chelation, gastric-pH, or transporter-competition absorption-interference mechanism, and documents no renal tubular, electrolyte, aldosterone-axis, or SIADH effect. None of Step 2's classical absorption-interference, enzyme-induction, or renal-wasting mechanisms is present by label review. This dossier's one classical-nutrient signal carried forward is the same narrow, theoretical, enzyme-localized mechanism its sibling MAO-B inhibitor selegiline carries in this project's companion dossier (B009): irreversible "suicide inhibition" of MAO-B proceeds by covalently engaging the flavin adenine dinucleotide (FAD) cofactor bound in the enzyme's active site, a mechanism a direct computational study names for rasagiline specifically (alongside selegiline), but one that inactivates individual MAO-B protein molecules rather than one shown anywhere in this review to measurably draw down whole-body riboflavin or FAD status. It is graded yellow, theoretical only, and that computational source is flagged in the Overlap map as shared with the Selegiline sibling dossier rather than as two independent confirmations.

selective MAO-B inhibitor (irreversible, propargylamine) · ATC N04BD02 · also sold as Azilect and generic rasagiline mesylate tablets · reviewed 2026-10-02. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Rasagiline in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
Two or more independent Tier A sources, this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit.
Yellow — Low
Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: Not gradeable under the rules above because nothing has been measured. Published as a documented gap, never as reassurance that there is no effect.

What the research found

General nutritional intake (anorexia/weight loss, bounded to adjunct-to-levodopa therapy)

Orange — Moderate

Evidence: bounded to combination-therapy population

In rasagiline's own placebo-controlled adjunct-to-levodopa trial, rasagiline-treated patients had materially higher rates of weight loss, anorexia, nausea, and vomiting than placebo, a genuine reduced-dietary-intake risk; the same excess was not reported in the monotherapy trial at the label's 3-percentage-point reporting threshold, bounding this finding to the combination-therapy population.

Full detail and limits

What the grade means here: At least one Tier A source with this drug in the cohort showing a real but bounded deficit: an exposure window, a subgroup, low frequency, or a functional rather than circulating deficit. Orange, bounded to combination-therapy population

Limits on what this shows

  • Key negative/null findings: The monotherapy trial did not surface the same magnitude of effect at the label's reporting threshold, suggesting levodopa co-therapy, disease severity, or dose-combination effects may drive most of the signal rather than rasagiline in isolation; this is disclosed as a limitation on attribution, not resolved.
  • At-risk subgroups: Patients on rasagiline as adjunct to levodopa, particularly those with pre-existing low body weight, swallowing difficulty, or reduced appetite from advancing Parkinson's disease itself (confounding by indication/disease stage, Hard Rule 6, cannot be excluded from trial-level adverse-event data alone).

Regulatory status

Tier A, drawn directly from the FDA-approved labeling's own placebo-controlled adverse-reaction tables (Table 3, adjunct-to-levodopa Study 3).

Population evidence

Randomized, placebo-controlled trial, rasagiline 1 mg/day as adjunct to levodopa (Study 3): weight loss 9% (rasagiline) vs 3% (placebo); anorexia 5% vs 1%; nausea 12% vs 8%; vomiting 7% vs 1%; dry mouth 6% vs 3%. In the monotherapy trial (Study 1), the label's own reporting threshold (reactions 3 percentage points or more above placebo) surfaced flu syndrome, arthralgia, depression, and dyspepsia, not weight loss or anorexia, indicating this reduced-intake signal is specifically bounded to, or at minimum concentrated in, the levodopa-combination population rather than monotherapy.

Mechanism

Named, Step 2 mechanism H (changed intake via appetite suppression, nausea, and dopaminergic/gastrointestinal effects), consistent with enhanced dopaminergic tone from combining a MAO-B inhibitor with levodopa. This is a reduced-caloric/micronutrient-intake risk factor, not a measured deficiency of any single named nutrient, and is framed as such.

Counter-evidence held on record

This is an intake-risk flag from passive adverse-event surveillance in a combination-therapy trial, not a dedicated nutrition or body-composition sub-study; it does not identify which specific micronutrients, if any, are affected, and disease-stage confounding (Hard Rule 6) is not excluded. This finding supports routine weight and appetite monitoring, not a specific supplement recommendation; no dose of any nutrient is implied or recommended by this entry.

Riboflavin / FAD (enzyme cofactor)

Yellow — Low

Evidence: theoretical, enzyme-localized

Rasagiline's irreversible, suicide-inhibition mechanism covalently engages the FAD cofactor bound inside MAO-B's active site, a real and well-described pharmacological mechanism confirmed computationally for rasagiline specifically, but one localized to individual enzyme molecules rather than demonstrated anywhere in this review to affect whole-body riboflavin or FAD status.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, theoretical, enzyme-localized

Limits on what this shows

  • Key negative/null findings: No clinical riboflavin-status study, in either direction, was located for rasagiline. The absence of any such study is itself notable and is flagged here rather than filled in with an assumption.
  • At-risk subgroups: None established.

Regulatory status

Not addressed in the FDA/DailyMed labeling; no riboflavin warning or monitoring requirement is named in the sections reached.

Population evidence

No clinical study was located measuring serum or red-cell riboflavin, FAD, or the erythrocyte glutathione reductase activation coefficient (the standard functional riboflavin marker) in rasagiline-treated patients. The supporting evidence is enzyme biochemistry/pharmacology, not a rasagiline patient cohort: Tandaric T, Prah A, Stare J, Mavri J, Vianello R. Hydride Abstraction as the Rate-Limiting Step of the Irreversible Inhibition of Monoamine Oxidase B by Rasagiline and Selegiline: A Computational Empirical Valence Bond Study. Int J Mol Sci. 2020 (PMID 32858935), naming rasagiline directly alongside selegiline. This source is identical to the one used for the equivalent entry in this project's Selegiline dossier (B009); that overlap is disclosed in the Overlap map below rather than treated as a second, independent rasagiline-specific confirmation.

Mechanism

Named, Tier B. MAO carries a covalently-bound FAD cofactor at its active site; rasagiline's irreversible MAO-B inhibition proceeds via a hydride-abstraction step engaging this flavin, per the cited computational study. This inactivates individual MAO-B protein molecules; new MAO-B protein incorporating fresh FAD is resynthesized over time using the cell's ordinary FAD pool.

Counter-evidence held on record

No study has measured riboflavin or FAD status in rasagiline-treated patients in either direction. This entry rests on a well-described enzyme mechanism shared with selegiline, not a clinical finding, and that gap is stated plainly rather than implied away. No supplementation dose is recommended at this grade. This is an intra-enzyme mechanism, not a demonstrated systemic nutrient-depletion pathway, and must not be read as evidence that rasagiline causes riboflavin deficiency.

  • Tandaric T, Prah A, Stare J, Mavri J, Vianello R. Hydride Abstraction as the Rate-Limiting Step of the Irreversible Inhibition of Monoamine Oxidase B by Rasagiline and Selegiline: A Computational Empirical Valence Bond Study. Int J Mol Sci. 2020. — Computational/mechanistic study, rasagiline and selegiline both named directly, PMID 32858935. Shared with the equivalent entry in this project's Selegiline dossier (B009); see Overlap map.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden

Yellow — Low

Direction: reverse direction (as labelled in the source) · Evidence: protective, reverse-direction, not a deficiency

A consistent, drug-specific body of preclinical evidence spanning more than two decades shows rasagiline itself stabilizes mitochondrial membrane potential, suppresses cytochrome c release and caspase-3 activation, and upregulates anti-apoptotic bcl-xL/Bcl-2 expression in neuronal cell models under toxic, ischemia-like, or apoptotic stress; this is rasagiline's own purported, investigational neuroprotective pharmacology, a protective signal and the opposite of a mitochondrial burden, graded here only because this protocol requires the category be addressed for every medication, every time.

Full detail, limits and 4 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, protective, reverse-direction, not a deficiency

Limits on what this shows

  • Key negative/null findings: No source located in this review contradicts the mitochondrial-protective direction for rasagiline itself. All located evidence is preclinical (cell culture); no human biomarker study was found in either direction.
  • At-risk subgroups: Not established; findings are from toxin-, ischemia-, or apoptosis-challenged neuronal cell models, not baseline healthy-tissue measurements, and do not translate directly to a patient population or subgroup.

Regulatory status

Not addressed in the FDA/DailyMed labeling; mitochondrial pharmacology is investigational and is not part of rasagiline's approved labeling basis (large disease-modification trials such as ADAGIO and TEMPO tested clinical endpoints, not mitochondrial biomarkers, and are not cited here as mitochondrial evidence).

Population evidence

Entirely preclinical, cell-culture models, drug-specific (rasagiline named directly in each title, not a class member): Naoi M, Maruyama W, Youdim MBH, et al. Molecular mechanism underlying neuroprotection by rasagiline. J Neurochem. 2002;81(s1):4 (DOI 10.1046/j.1471-4159.2002.00012.x), reporting rasagiline "stabilizes mitochondrial membrane potential and suppresses the apoptotic cascade" in SH-SY5Y cells challenged with dopaminergic neurotoxins, with selective upregulation of bcl-xL and no change in pro-apoptotic bax/bad. Naoi M, Maruyama W, Yi H. Rasagiline prevents apoptosis induced by PK11195...through suppression of cytochrome c release from mitochondria. J Neural Transm. 2013;120(11):1539-1551 (DOI 10.1007/s00702-013-1033-x), rasagiline tested directly in SH-SY5Y cells. Bar-Am O, Weinreb O, Amit T, Youdim MBH. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem. 2009;112(5):1131-1137 (DOI 10.1111/j.1471-4159.2009.06542.x), the active rasagiline metabolite contributing independently to the parent drug's anti-apoptotic effect. Lecht S, et al. (Lazarovici P, senior author). Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling. Biomedicines. 2024;12(7):1592 (PMID 39062165), rasagiline 3-10 microM tested directly in PC12 cells, reducing mitochondrial ROS production by approximately 15% and increasing Akt phosphorylation by approximately 50% alongside 80% neuroprotection against OGD/reoxygenation injury. None of this evidence is a human clinical trial; no study in this review directly measured mitochondrial membrane potential in rasagiline-treated patient tissue.

Mechanism

Named. Rasagiline's propargylamine structure is reported by its own investigators to act through a mechanism independent of MAO-B inhibition itself, involving stabilization of the mitochondrial permeability transition, suppression of cytochrome c release, and transcriptional upregulation of anti-apoptotic Bcl-2-family proteins.

Counter-evidence held on record

All located evidence runs protective; no source shows rasagiline causing mitochondrial harm. The evidence base is entirely preclinical cell culture, and no human trial in this review directly confirms the mechanism in patients. This is a protective, reverse-direction finding describing rasagiline's own purported, investigational pharmacology (Hard Rule 2), not a depletion risk, and must never be recast as one. It must never be read as implying mitochondrial-support supplementation (CoQ10, L-carnitine, alpha-lipoic acid, or similar) is indicated or needed, or that rasagiline itself otherwise causes mitochondrial harm. No supplementation is implied or recommended by this entry.

  • Naoi M, Maruyama W, Youdim MBH, et al. Molecular mechanism underlying neuroprotection by rasagiline. J Neurochem. 2002;81(s1):4. — Mechanistic study abstract, SH-SY5Y cells, rasagiline named directly, DOI 10.1046/j.1471-4159.2002.00012.x Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, authors, and a reconstructed abstract); the publisher's own page was not separately opened. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, authors, and a reconstructed abstract); the publisher's own page was not separately opened. PMID not independently confirmed in this review.
  • Bar-Am O, Weinreb O, Amit T, Youdim MBH. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem. 2009;112(5):1131-1137. — Mechanistic review, rasagiline's active metabolite, DOI 10.1111/j.1471-4159.2009.06542.x Access note: confirmed via an OpenAlex single-record lookup by DOI; the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI; the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.
  • Naoi M, Maruyama W, Yi H. Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria. J Neural Transm (Vienna). 2013;120(11):1539-1551. — Mechanistic study, SH-SY5Y cells, rasagiline named directly, DOI 10.1007/s00702-013-1033-x Access note: confirmed via an OpenAlex single-record lookup by DOI; the Springer publisher page itself was not separately opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI; the Springer publisher page itself was not separately opened in full. PMID not independently confirmed in this review.
  • Lecht S, et al. (Lazarovici P, senior/corresponding author). Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling. Biomedicines. 2024;12(7):1592. — PC12 cell model, rasagiline (3-10 microM) tested directly, PMID 39062165, DOI 10.3390/biomedicines12071592

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress

Yellow — Low

Direction: reverse direction (as labelled in the source) · Evidence: protective, reverse-direction, not a deficiency

The same drug-specific preclinical literature shows rasagiline activates Akt/Nrf2 signaling and upregulates antioxidant-enzyme expression (NQO1, HO-1, catalase) while reducing mitochondrial reactive-oxygen-species production in a neuronal cell model; this is rasagiline's own purported antioxidant pharmacology, protective and the opposite of a deficiency, graded here only because this protocol requires the category be addressed for every medication, every time.

Full detail, limits and 3 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, protective, reverse-direction, not a deficiency

Limits on what this shows

  • Key negative/null findings: No source located in this review shows rasagiline raising oxidative-stress markers; all confirmed directions are protective. No human biomarker study (e.g., serum malondialdehyde or glutathione in rasagiline-treated patients) was located in either direction.
  • At-risk subgroups: Not established.

Regulatory status

Not addressed in the FDA/DailyMed labeling for rasagiline; antioxidant pharmacology is investigational, not part of the approved labeling basis.

Population evidence

In vitro, drug-specific: Lecht S, et al. Biomedicines. 2024;12(7):1592 (PMID 39062165), rasagiline (3-10 microM) tested directly in PC12 cells under oxygen-glucose deprivation/reoxygenation: mitochondrial ROS production decreased approximately 15%, Nrf2 nuclear translocation increased 40-90%, antioxidant enzyme mRNA (NQO1, HO-1, catalase) elevated 1.8- to 2.0-fold, and alpha-synuclein protein expression decreased approximately 50%. Maruyama W, Yamamoto T, Kitani K, Carrillo MC, Youdim MBH, Naoi M. Mechanism underlying anti-apoptotic activity of a (-)deprenyl-related propargylamine, rasagiline. Mech Ageing Dev. 2000;116(2-3):181-191 (PMID 10996018), rasagiline tested directly, mechanistic apoptosis-protection study referencing oxidative-stress-linked caspase activation. Naoi M, Maruyama W, Youdim MBH, et al. Molecular Basis of Neuroprotective Activities of Rasagiline and the Anti-Alzheimer Drug TV3326. Cell Mol Neurobiol. 2001;21(6):555-573 (PMID 12043833), rasagiline named directly alongside the structurally related TV3326.

Mechanism

Named, Tier B. Rasagiline's propargylamine structure is reported to activate pro-survival Akt signaling, driving Nrf2 nuclear translocation and transcriptional induction of phase-II antioxidant/detoxification enzymes, independent of and in addition to its mitochondrial-membrane-stabilizing effect (see Overlap map).

Counter-evidence held on record

No source located in this review shows rasagiline increasing oxidative stress; the confirmed direction is protective, and this is entirely preclinical evidence. This is a protective, reverse-direction finding describing rasagiline's own purported, investigational pharmacology (Hard Rule 2), not a nutrient deficiency, and must never be recast as one. No antioxidant supplementation is implied, needed, or supported by this entry.

  • Naoi M, Maruyama W, Youdim MBH, et al. Molecular Basis of Neuroprotective Activities of Rasagiline and the Anti-Alzheimer Drug TV3326. Cell Mol Neurobiol. 2001;21(6):555-573. — Mechanistic review, rasagiline named directly, PMID 12043833
  • Maruyama W, Yamamoto T, Kitani K, Carrillo MC, Youdim MBH, Naoi M. Mechanism underlying anti-apoptotic activity of a (-)deprenyl-related propargylamine, rasagiline. Mech Ageing Dev. 2000;116(2-3):181-191. — Mechanistic study, rasagiline named directly, PMID 10996018
  • Lecht S, et al. (Lazarovici P, senior/corresponding author). Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling. Biomedicines. 2024;12(7):1592. — PC12 cell model, rasagiline (3-10 microM) tested directly, PMID 39062165, DOI 10.3390/biomedicines12071592

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Copper

Not graded — disclosed evidence gap

Evidence: tooling-limited

No grade assigned: no rasagiline-specific evidence could be confirmed at any tier this session, and no circulating consumer claim could be verified to rebut as white, primarily because the literature-search channels needed for this category were rate-limited partway through this review.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded, tooling-limited

Limits on what this shows

  • Why no grade: Original pass: a PubMed search-listing fetch for "rasagiline copper" returned a response whose rendering was internally inconsistent (it reported both a large generic-copper result set and a note that the term "rasagiline" itself was not matched), treated as unreliable rather than a genuine result. Follow-up attempts via the Europe PMC REST API, the Crossref works-search endpoint, the Semantic Scholar Graph API, and OpenAlex's works-search endpoint for "rasagiline copper," "rasagiline ceruloplasmin," and "rasagiline serum copper" were all refused with HTTP 429 before returning content. Repair pass (2026-10-02): the same PubMed unreliable-render problem reproduced exactly (PubMed again silently substituted "asagiline" and served generic copper-physiology results, e.g. "Copper deficiency anemia," "Copper metabolism," with no rasagiline-specific hit visible). The Crossref works-search endpoint did respond this time, for two phrasings ("rasagiline copper" and "rasagiline copper zinc trace element"), and returned only generic rasagiline regulatory/pharmacology records (USP monographs, EPAR summaries, case reports unrelated to copper) with no copper-specific content, a clean non-match rather than a block. Fresh attempts at Europe PMC, the Semantic Scholar Graph API, and OpenAlex's works-search endpoint were all again refused with HTTP 429. No circulating consumer claim regarding rasagiline and copper could be identified either pass, because the Step 6 consumer-web sweep was not reachable: this session's shared WebSearch tool budget was exhausted on both the original review and a direct retry during this repair pass.

Assessment

Still disclosed as a tooling-bounded gap rather than a fully confirmed clean literature search: PubMed and Crossref have now each been tried on two separate passes with multiple phrasings, and Crossref's clean non-match adds modest weight toward a genuine gap, but PubMed's rendering problem has reproduced twice and Europe PMC, Semantic Scholar, and OpenAlex works-search have never successfully returned a result for this category across either pass. A future revision should re-attempt those three specific channels once broader access is available; OpenAlex and Crossref single-record lookups by DOI/PMID (which do work) cannot substitute for a keyword search when no candidate DOI/PMID is already in hand.

Iron

Not graded — disclosed evidence gap

See study details

No grade assigned: no rasagiline-specific iron-status evidence exists, and the only nearby literature located fails the Hard Rule 6 cohort test. Parkinson's disease's own disease-intrinsic brain iron accumulation is explicitly not attributed to rasagiline here (Hard Rule 2).

Full detail, limits and 3 references

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: Original pass: two sources were located and opened directly: Zheng H, Fridkin M, Youdim MBH. Site-Activated Chelators Derived from Anti-Parkinson Drug Rasagiline as a Potential Safer and More Effective Approach to the Treatment of Alzheimer's Disease. Neurochem Res. 2010 (DOI 10.1007/s11064-010-0293-1), which describes new hybrid prochelator compounds (HLA20A, M30D) built by "merging the important pharmacophores of rasagiline, rivastigmine, and donepezil" into single new molecules, not rasagiline itself. Bar-Am O, Amit T, Kupershmidt L, et al. Neuroprotective and neurorestorative activities of a novel iron chelator-brain selective monoamine oxidase-A/monoamine oxidase-B inhibitor in animal models of Parkinson's disease and aging. Neurobiol Aging. 2015 (DOI 10.1016/j.neurobiolaging.2014.10.026), which describes VAR10303, a new compound "chemically hybridizing" rasagiline's N-propargyl moiety with a different iron-chelating pharmacophore (from VK-28), again not rasagiline itself. Both fail the Hard Rule 6 cohort test. Repair pass (2026-10-02): a fuller PubMed search-listing fetch for "rasagiline iron" rendered correctly this time (37 total results, no term dropped) and confirmed the same pattern at scale: the top results are dominated by rasagiline-derived hybrid chelator/multi-target compounds (the Zheng and Bar-Am sources above, plus further related titles such as "Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28" (2005) and "Iron-chelating backbone coupled with monoamine oxidase inhibitory moiety" (2011)), every one of them a new hybrid molecule built on rasagiline's scaffold, not rasagiline itself, and one class-level review ("Monoamine oxidase inhibitors, and iron chelators in depressive illness," 2018) that is not drug-specific. A further candidate was identified via Crossref: Mandel SA, Weinreb O, Amit T, Youdim MBH. Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. Brain Res Rev. 2005;48(2):379-387 (DOI 10.1016/j.brainresrev.2004.12.027). Its OpenAlex metadata record (opened directly) flags "iron chelation" as an indexed keyword/topic, but the article's full text sits behind an Elsevier paywall that this review could not open, and the title itself covers "rasagiline and its derivatives" jointly, so whether any iron-related claim in it applies to rasagiline itself or only to its derivatives could not be verified. Per the rule against citing a source not actually opened and read, this review does not treat it as supporting evidence either way; it is disclosed here as an unresolved lead for a future revision with full-text access, not as a finding. Brain iron accumulation in Parkinson's disease remains well-documented disease-intrinsic pathology, not a rasagiline effect, and stays deliberately excluded from grading per Hard Rule 2. No circulating consumer claim regarding rasagiline and iron (depletion or overload) could be identified on either pass; the Step 6 consumer-web sweep was not reachable for the reasons stated under Copper above.

Assessment

A genuine, now more thoroughly confirmed negative result for rasagiline-specific iron-status evidence: the adjacent drug-design literature is real, substantial, and has now been surveyed at a larger scale (37 PubMed results), and it still does not pass the Hard Rule 6 cohort test for rasagiline itself; that remains the main finding of this entry. The one open question is the Mandel 2005 review's full text, which this review could not access on either pass; a future revision with full-text or library access to Brain Research Reviews should open it specifically to resolve whether it attributes any iron-chelating property to rasagiline itself or only to its derivatives.

  • Zheng H, Fridkin M, Youdim MBH. Site-Activated Chelators Derived from Anti-Parkinson Drug Rasagiline as a Potential Safer and More Effective Approach to the Treatment of Alzheimer's Disease. Neurochem Res. 2010. — New hybrid prochelator compounds (HLA20A, M30D), DOI 10.1007/s11064-010-0293-1 Cohort note: the chelator compounds described are new molecules built using rasagiline's chemical scaffold as a design template, not rasagiline itself; fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.Cohort note: the chelator compounds described are new molecules built using rasagiline's chemical scaffold as a design template, not rasagiline itself; fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.
  • Bar-Am O, Amit T, Kupershmidt L, et al. Neuroprotective and neurorestorative activities of a novel iron chelator-brain selective monoamine oxidase-A/monoamine oxidase-B inhibitor in animal models of Parkinson's disease and aging. Neurobiol Aging. 2015. — New compound VAR10303, DOI 10.1016/j.neurobiolaging.2014.10.026 Cohort note: VAR10303 is a new molecule chemically hybridizing rasagiline's N-propargyl moiety with a separate iron-chelating pharmacophore; not rasagiline itself, fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.Cohort note: VAR10303 is a new molecule chemically hybridizing rasagiline's N-propargyl moiety with a separate iron-chelating pharmacophore; not rasagiline itself, fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.
  • Mandel SA, Weinreb O, Amit T, Youdim MBH. Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. Brain Res Rev. 2005;48(2):379-387. — Review, DOI 10.1016/j.brainresrev.2004.12.027. Identified during the 2026-10-02 repair pass as a candidate Iron-entry source; its OpenAlex metadata record flags "iron chelation" as an indexed topic Access note: only the OpenAlex metadata record (title, authors, year, venue) could be opened; the full text is behind an Elsevier paywall (linkinghub.elsevier.com redirect) and could not be read, so whether its iron-chelation content applies to rasagiline itself or only to its derivatives could not be verified. Not relied upon as supporting evidence per the rule against citing an unopened source; listed to disclose the lead for a future revision.Access note: only the OpenAlex metadata record (title, authors, year, venue) could be opened; the full text is behind an Elsevier paywall (linkinghub.elsevier.com redirect) and could not be read, so whether its iron-chelation content applies to rasagiline itself or only to its derivatives could not be verified. Not relied upon as supporting evidence per the rule against citing an unopened source; listed to disclose the lead for a future revision.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Yellow — Low

Evidence: mechanistically adjacent, motility not composition

A drug-specific rat study found long-term rasagiline treatment reduces colonic motility by elevating colonic dopamine content and activating dopamine D1 receptors; this is mechanistically adjacent to gut microbiome risk through altered colonic transit time (Step 2 mechanism A), a plausible pathway since slowed transit is independently associated with shifts in colonic bacterial composition in the general physiology literature, but the cited study measured motility and dopamine content, not microbiome composition or diversity directly, and that distinction is kept explicit here.

Full detail, limits and 1 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, mechanistically adjacent, motility not composition

Limits on what this shows

  • Key negative/null findings: None located measuring microbiome composition or diversity with rasagiline in either direction; this is the central gap in this entry, stated plainly rather than inferred away.
  • At-risk subgroups: Not established for microbiome composition specifically; constipation from slowed colonic transit is a generally recognized risk in Parkinson's disease patients on dopaminergic therapy broadly (confounding by indication/co-therapy, Hard Rule 6, not excluded).

Regulatory status

Not addressed in the FDA/DailyMed labeling; constipation/GI motility effects are not flagged as a labeled adverse reaction distinct from the general dopaminergic-overlap adverse-reaction profile.

Population evidence

Animal, drug-specific (rasagiline named directly, not a class member): Liu C, Zhang XL, Zhou L, Wang T, Quan Z, Zhang Y, Li J, Li GW, Zheng LF, Li LS, Zhu JX. Rasagiline, an inhibitor of MAO-B, decreases colonic motility through elevating colonic dopamine content. Neurogastroenterol Motil. 2018 (DOI 10.1111/nmo.13390), rat model, long-term rasagiline treatment reduced colonic motility via dopamine D1 receptor activation and increased colonic dopamine content. This finding was confirmed via a bibliographic record lookup (title, year, journal, full author list, and a reconstructed abstract summary); the full-text article page itself returned an HTTP 403 error on direct fetch and could not be opened in full, so granular effect sizes beyond the summary above are not independently confirmed and are not claimed here.

Mechanism

Named, Tier B, but one step removed from the category's core definition. Elevated colonic dopamine (from reduced local MAO-B-mediated breakdown) slows colonic transit via D1 receptor activation; slowed colonic transit is a recognized driver of shifts in gut bacterial composition in the broader gastroenterology literature (Step 2 mechanism A, altered transit time), but no study located in this review measured that downstream microbiome step directly in rasagiline-exposed animals or patients.

Counter-evidence held on record

No study located directly measures gut microbiome composition or diversity in rasagiline-exposed subjects; the confirmed finding is motility/transit-level, one mechanistic step removed from the microbiome itself, and that gap is disclosed rather than bridged by inference presented as fact. This entry describes a plausible, drug-specific motility mechanism, not a demonstrated microbiome-composition change and not a nutrient deficiency. No probiotic, prebiotic, or other microbiome-targeted supplementation is implied or recommended.

  • Liu C, Zhang XL, Zhou L, Wang T, Quan Z, Zhang Y, Li J, Li GW, Zheng LF, Li LS, Zhu JX. Rasagiline, an inhibitor of MAO-B, decreases colonic motility through elevating colonic dopamine content. Neurogastroenterol Motil. 2018. — Rat model, rasagiline named directly, DOI 10.1111/nmo.13390 Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, full author list, and a reconstructed abstract); the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, full author list, and a reconstructed abstract); the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production

Yellow — Low

Evidence: protective, indirect, theoretical

The same mitochondrial-membrane-potential-preserving literature cited under Mitochondrial burden is mechanistically relevant to ATP-generating capacity, since membrane potential is the proton-motive force ATP synthase depends on, but no study located in this review directly measured cellular or mitochondrial ATP content or synthesis rate with rasagiline, so this entry is graded as an indirect, theoretical signal, weaker than and kept independent from the Mitochondrial burden entry per Hard Rule 7.

Full detail, limits and 4 references

What the grade means here: Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) with no drug-specific human status data; also used for context flags and interactions running the other direction. Yellow, protective, indirect, theoretical

Limits on what this shows

  • Key negative/null findings: None located; the gap is the direct-measurement gap itself, disclosed here rather than papered over with the adjacent membrane-potential findings.
  • At-risk subgroups: Not established.

Regulatory status

Not addressed in the FDA/DailyMed labeling.

Population evidence

Same preclinical sources as Mitochondrial burden: Naoi et al. 2002 (DOI 10.1046/j.1471-4159.2002.00012.x); Naoi, Maruyama, Yi 2013 (DOI 10.1007/s00702-013-1033-x); Bar-Am et al. 2009 (DOI 10.1111/j.1471-4159.2009.06542.x); Lecht et al. 2024 (PMID 39062165); shared origin disclosed in the Overlap map below. None of these studies report ATP content, ATP synthesis rate, or oxygen-consumption-based energy flux directly; all measure mitochondrial membrane potential, cytochrome c release, or ROS production as their endpoint.

Mechanism

Inferred, not directly demonstrated. Preserved mitochondrial membrane potential is mechanistically upstream of ATP synthase function in standard mitochondrial physiology, but this review found no direct ATP measurement confirming that the inference translates into altered cellular energy output in rasagiline-exposed tissue.

Counter-evidence held on record

No source located measures ATP content or synthesis rate in rasagiline-exposed tissue in either direction; this entry rests entirely on mechanistic inference from the membrane-potential literature shared with Mitochondrial burden, and that inferential gap is stated plainly. This is an indirect, mechanistically inferred signal, explicitly weaker than Mitochondrial burden above it, and must not be read as a demonstrated energy-production benefit or as grounds for any energy-metabolism supplement claim (CoQ10, creatine, B vitamins, or similar). No supplementation is implied or recommended.

  • Naoi M, Maruyama W, Youdim MBH, et al. Molecular mechanism underlying neuroprotection by rasagiline. J Neurochem. 2002;81(s1):4. — Mechanistic study abstract, SH-SY5Y cells, rasagiline named directly, DOI 10.1046/j.1471-4159.2002.00012.x Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, authors, and a reconstructed abstract); the publisher's own page was not separately opened. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, authors, and a reconstructed abstract); the publisher's own page was not separately opened. PMID not independently confirmed in this review.
  • Bar-Am O, Weinreb O, Amit T, Youdim MBH. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem. 2009;112(5):1131-1137. — Mechanistic review, rasagiline's active metabolite, DOI 10.1111/j.1471-4159.2009.06542.x Access note: confirmed via an OpenAlex single-record lookup by DOI; the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI; the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.
  • Naoi M, Maruyama W, Yi H. Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria. J Neural Transm (Vienna). 2013;120(11):1539-1551. — Mechanistic study, SH-SY5Y cells, rasagiline named directly, DOI 10.1007/s00702-013-1033-x Access note: confirmed via an OpenAlex single-record lookup by DOI; the Springer publisher page itself was not separately opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI; the Springer publisher page itself was not separately opened in full. PMID not independently confirmed in this review.
  • Lecht S, et al. (Lazarovici P, senior/corresponding author). Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling. Biomedicines. 2024;12(7):1592. — PC12 cell model, rasagiline (3-10 microM) tested directly, PMID 39062165, DOI 10.3390/biomedicines12071592

Oxygen delivery/utilization

Not graded — disclosed evidence gap

Evidence: tooling-limited

No grade assigned: a real Tier A null safety signal exists from rasagiline's own placebo-controlled trials, but no Tier B/C mechanistic evidence and no circulating consumer claim were confirmed to support even a theoretical grade, in substantial part because keyword-search channels for this category were rate-limited.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded, tooling-limited

Limits on what this shows

  • Why no grade: Rasagiline's own FDA adverse-reaction tables (monotherapy Study 1 and adjunct-to-levodopa Study 3) report no hematologic adverse reaction (anemia, hemoglobin, or hematocrit change) at any reporting threshold; this is a real, if passive, Tier A null signal, recorded here rather than silently omitted, but a null finding from general safety surveillance cannot itself satisfy the Tier B/C bar Step 7 requires for even a yellow grade. Original pass: a PubMed search-listing fetch for "rasagiline hemoglobin OR erythropoietin OR hematocrit" returned only generic, decades-old erythropoietin-physiology results with no rasagiline-specific hit, treated as an unreliable, likely mis-parsed result rather than a confirmed clean negative. Subsequent attempts via Europe PMC, Crossref works-search, Semantic Scholar, and OpenAlex works-search were all refused with HTTP 429. Repair pass (2026-10-02): PubMed's own interface returned an explicit, unambiguous "Your search for rasagiline anemia retrieved no results" message, a genuine clean-zero result rather than a mis-parsed one, though a separate "rasagiline hemoglobin" query again reproduced the unreliable, term-dropping render seen under Copper and could not be trusted. The Crossref works-search endpoint responded this time for "rasagiline hemoglobin hematocrit" and returned only generic hematology methods literature (point-of-care hemoglobin assays, athlete weight-cutting studies, postmenopausal hematocrit norms), with no rasagiline-specific hit, again a clean non-match. Fresh attempts via Europe PMC, Semantic Scholar, and OpenAlex works-search for hemoglobin/hematocrit/erythropoietin phrasings were all again refused with HTTP 429. No circulating consumer claim regarding rasagiline and oxygen delivery, hemoglobin, or red-cell parameters could be identified on either pass; the Step 6 consumer-web sweep was not reachable for the reasons stated under Copper above.

Assessment

A real, reassuring-but-not-dispositive Tier A null finding from the label's passive adverse-event surveillance, now corroborated by two independently clean results (PubMed's explicit "no results" message for "rasagiline anemia," and Crossref's clean non-match for hemoglobin/hematocrit terms), while Europe PMC, Semantic Scholar, and OpenAlex works-search remain genuinely tooling-blocked across both passes and have never been checked. This should still not be reworded as "rasagiline is safe for oxygen delivery," only as "no hematologic signal was reported in rasagiline's own clinical trials, two independent keyword-search channels returned clean non-matches, and three further channels remain unchecked due to rate-limiting."

Claims checked and not supported

These circulate online for this medication. They are listed here only so they can be answered, never as findings, and they are not graded.

A claim with no supporting evidence is not necessarily disproven. Where evidence actually argues against a claim, that is stated below.

  • Rasagiline requires the same tyramine-restricted ("MAOI diet") that older, non-selective MAO inhibitors require

    Where it comes from: A plausible consumer mischaracterization pattern: because rasagiline is an MAO inhibitor, and because the tyramine-restricted diet is widely associated with MAO inhibitors as a drug class (and is required for selegiline at its higher, non-selective transdermal doses, per this project's Selegiline dossier, B009), it is easily, and incorrectly, assumed to apply identically to rasagiline at its recommended doses.

    Why it fails: Rasagiline's own FDA/DailyMed labeling states plainly: "Dietary tyramine restriction is not required during treatment with recommended doses" of rasagiline (0.5 mg or 1 mg once daily), with "no cases of hypertensive crisis in the clinical development program associated with 1 mg daily AZILECT treatment." Only meals containing very large amounts of tyramine (over 150 mg) are flagged for caution, because rasagiline's selectivity for MAO-B over MAO-A is preserved at these doses. This is a labeled, drug-specific, dose-dependent fact that directly contradicts the generalized class claim for rasagiline at recommended exposure (Hard Rule 6, class extrapolation fails the cohort test here), and is not a nutrient-deficiency matter in any case.

  • Rasagiline (or "Parkinson's medications" generally) depletes vitamin B12 and folate and raises homocysteine

    Where it comes from: A real, well-documented finding in Parkinson's disease, generalized from "dopaminergic medications" broadly to the specific drug a reader happens to be taking. Meta-analyses confirm PD patients have significantly elevated homocysteine (SMD 0.80) and reduced B12 (SMD -0.33) and folate (SMD -0.13) versus controls, and that "dopaminergic medications treated patients" show higher homocysteine than untreated patients.

    Why it fails: The mechanism underlying this signal is catechol-O-methyltransferase (COMT)-mediated O-methylation of levodopa, which consumes S-adenosylmethionine as a methyl donor and raises homocysteine; this pathway requires a catechol substrate. Rasagiline is an indanyl propargylamine with no catechol structure and is metabolized via CYP1A2, not COMT, so it is not a substrate for this pathway and this specific mechanism does not apply to rasagiline. The cited meta-analysis (Features of Plasma Homocysteine, Vitamin B12, and Folate in Parkinson's Disease: An Updated Meta-Analysis, J Integr Neurosci, 2023) examines "dopaminergic medications" as a single undifferentiated group (overwhelmingly levodopa-based regimens in real-world practice) and does not isolate MAO-B inhibitors or rasagiline as a distinct studied subgroup; no Tier A or Tier B source located in this review measures homocysteine, B12, or folate in rasagiline-monotherapy patients specifically. This is confounding by indication/co-therapy (Hard Rule 6) and a chemistry-based mechanism mismatch (Step 7 white-tier boundary: "this drug's specific chemistry...rules the mechanism out"), not a verified rasagiline effect.

How the body handles this medication

Metabolism and CYP enzymes
Rasagiline "undergoes almost complete biotransformation in the liver prior to excretion," via N-dealkylation and/or hydroxylation, "with CYP1A2 being the major isoenzyme involved in rasagiline metabolism." The label states rasagiline "is unlikely to cause any clinically significant interference" with substrates of CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4, or 4A -- it is a CYP1A2 substrate, not a clinically meaningful inducer or inhibitor of these enzymes. Co-administration with ciprofloxacin, a CYP1A2 inhibitor, increased rasagiline AUC by 83%; patients on ciprofloxacin or other CYP1A2 inhibitors should not exceed 0.5 mg/day.FDA prescribing information, rasagiline tablets (NDA/ANDA 201971), accessdata.fda.gov label, 2017, Clinical Pharmacology and Dosage and Administration sections
Elimination and renal/hepatic impairment
Elimination occurs "primarily via urine and secondarily via feces" (62% of total dose in urine, 7% in feces, over 7 days); "less than 1% of rasagiline was excreted as unchanged drug in urine," with glucuronide conjugation of rasagiline and its metabolites as the major elimination pathway. No dose adjustment is needed in mild or moderate renal impairment (not studied in severe renal impairment or end-stage renal disease). Mild hepatic impairment requires capping the dose at 0.5 mg/day (AUC/Cmax increased 2-fold/1.4-fold); rasagiline "should not be used in patients with moderate or severe hepatic impairment" (AUC/Cmax increased 7-fold/2-fold in moderate impairment).FDA prescribing information, rasagiline tablets, Clinical Pharmacology and Use in Specific Populations sections
Absorption, food effect, and protein binding
Rasagiline is rapidly absorbed (Tmax approximately 1 hour); absolute bioavailability is about 36%. A high-fat meal decreases Cmax by approximately 60% and AUC by approximately 20% without changing Tmax; because AUC is not significantly affected, the label states rasagiline "can be administered with or without food," a food-to-drug absorption effect (dosing-timing note per Hard Rule 4), not evidence that rasagiline interferes with nutrient absorption. Plasma protein binding ranges 88-94%, with mean volume of distribution at steady state 87 L.FDA prescribing information, rasagiline tablets, Clinical Pharmacology section
Enzyme-cofactor mechanism (irreversible MAO-B inhibition)
Rasagiline is a selective, irreversible MAO-B inhibitor; MAO is "a flavin-containing enzyme...localized in mitochondrial membranes throughout the body" per the label. A direct computational (empirical valence bond) study names rasagiline specifically, alongside selegiline, in showing hydride abstraction from the covalently-bound FAD cofactor as the rate-limiting step of this irreversible, active-site-localized inhibition. This is the mechanistic basis of the Riboflavin/FAD entry below, graded theoretical because it is an intra-enzyme interaction, not a demonstrated systemic cofactor-depletion pathway.FDA prescribing information, rasagiline tablets, Clinical Pharmacology (12.1) section; Tandaric T, Prah A, Stare J, Mavri J, Vianello R. Int J Mol Sci. 2020 (PMID 32858935)
Tyramine and dietary amine interaction
"Dietary tyramine restriction is not required during treatment with recommended doses" of rasagiline (0.5 mg or 1 mg once daily); "there were no cases of hypertensive crisis in the clinical development program associated with 1 mg daily AZILECT treatment." Only meals containing "very high amounts (i.e., more than 150 mg) of tyramine" are flagged for caution, and "selectivity for inhibiting MAO-B diminishes in a dose-related manner as the dose is progressively increased above the recommended daily doses." This is a materially different, less restrictive labeling position than selegiline's at non-selective exposure, addressed directly in Fails verification below.FDA prescribing information, rasagiline tablets, Warnings and Precautions (5.1) and Patient Counseling (7.7) sections
Electrolytes, hematology, and routine laboratory monitoring
Neither the AZILECT nor the generic rasagiline labeling documents an electrolyte, SIADH, or aldosterone-axis effect, and no hematologic adverse reaction (anemia, hemoglobin, or hematocrit change) appears in the placebo-controlled adverse-reaction tables reviewed. This is a real but passive Tier A null signal, noted under Oxygen delivery/utilization below, not a dedicated biomarker study and not by itself sufficient to support a grade.FDA prescribing information, rasagiline tablets, Adverse Reactions (6.1) section, Tables 1 and 3

What the research says is worth watching

General information from the medication label and the studies above. It is not personal medical advice, and any change belongs with your prescriber.

  • Nutritional, bounded

    Weight and appetite monitoring on combination therapy

    Monitor body weight and appetite in patients starting rasagiline as adjunct to levodopa, where the labeled rate of weight loss (9% vs 3% placebo) and anorexia (5% vs 1% placebo) was materially higher than in monotherapy. This is a general-intake risk flag, not a specific-nutrient repletion measure, and should not be reframed as correcting a named deficiency.

  • Clinical, dosing

    CYP1A2 inhibitors and hepatic impairment dose caps

    Rasagiline exposure rises substantially with CYP1A2 inhibitors (ciprofloxacin: AUC +83%) and with hepatic impairment (mild: dose capped at 0.5 mg/day; moderate/severe: contraindicated). Not a nutrient-depletion pathway, but a real, labeled exposure-management requirement included here as context.

  • Clinical, dietary

    Tyramine caution without a standing dietary restriction

    No dietary tyramine restriction is required at recommended rasagiline doses; counsel patients only to avoid meals containing very large amounts (over 150 mg) of tyramine, and never extend selegiline's or older MAOIs' stricter dietary rules to rasagiline by default (see Fails verification).

  • Nutritional, theoretical

    Riboflavin awareness, not a standing recommendation

    Rasagiline's FAD-cofactor-engaging mechanism is real chemistry but enzyme-localized, with no study located measuring a resulting change in riboflavin status. This is not a reason for routine rasagiline-specific riboflavin testing or supplementation; no dose is recommended by this dossier.

  • Re-review trigger

    Re-search Copper, Iron, and Oxygen delivery/utilization

    A 2026-10-02 repair pass re-searched all three categories: PubMed and Crossref responded this time and returned clean, non-matching results for Copper and Oxygen delivery/utilization (plus an explicit PubMed "no results" message for "rasagiline anemia") and confirmed the Iron cohort-test failure at a larger scale (37 PubMed results, all hybrid-chelator molecules or class-level reviews). Europe PMC, the Semantic Scholar Graph API, and OpenAlex's works-search endpoint, however, were refused with HTTP 429 on both this pass and the original review and have never successfully returned a result for any of the three categories; a future revision should prioritize those three specific channels once broader access is available. For Iron specifically, a next revision should also try to obtain full-text access to Mandel SA et al., Brain Res Rev. 2005;48(2):379-387 (DOI 10.1016/j.brainresrev.2004.12.027), whose metadata flags "iron chelation" as a topic but which this review could not open past its abstract-free metadata stub.

Overlap map, to prevent double counting

  • Mitochondrial burden

    Shares evidence with: Oxidative stress, ATP production

    Note: All three yellow-tier physiological-category entries draw on the same drug-specific Naoi/Maruyama/Youdim/Weinreb/Lazarovici propargylamine-pharmacology research tradition, and one single 2024 source (Lecht S, et al., Biomedicines, PMID 39062165) directly supports both the Mitochondrial burden entry (mitochondrial ROS reduction) and the Oxidative stress entry (Akt/Nrf2 activation, antioxidant-enzyme induction) from the very same PC12-cell experiment. ATP production is explicitly the weaker, indirectly-inferred extension of the Mitochondrial burden finding, not a second, independent line of evidence. A reader should not count these overlapping sources as independently confirming all three entries.

  • Riboflavin / FAD (enzyme cofactor)

    Shares evidence with: Selegiline dossier (B009), Riboflavin / FAD entry

    Note: Cross-dossier overlap. Both this entry and the equivalent entry in this project's Selegiline dossier (B009) rest on the identical primary mechanistic source, Tandaric T, Prah A, Stare J, Mavri J, Vianello R. Int J Mol Sci. 2020 (PMID 32858935), a single computational study that names rasagiline and selegiline together in the same hydride-abstraction mechanism. A reader comparing the two sibling dossiers should not treat this as two independent confirmations of the FAD-cofactor mechanism; it is one source applied once to each of two MAO-B inhibitors it directly studied.

  • Gut microbiome risk

    Shares evidence with: (no overlap)

    Note: This entry rests on a single, distinct source (Liu et al. 2018, colonic motility/dopamine) not shared with any other entry in this dossier or, to this reviewer's knowledge, with any sibling dossier in the series.

All references used above
  1. AZILECT (rasagiline mesylate) tablet, prescribing information — DailyMed, setid a40d0e73-3f9f-4b01-979d-402c9cdaeb60, Clinical Pharmacology, Warnings and Precautions, and Patient Counseling Information sections
  2. Rasagiline tablet, FDA prescribing information (NDA/ANDA 201971) — accessdata.fda.gov label PDF, 2017, Clinical Pharmacology, Dosage and Administration, Use in Specific Populations, and Adverse Reactions (Tables 1 and 3) sections
  3. WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index — N04BD02, rasagiline (DDD 1 mg, oral)
  4. Tandaric T, Prah A, Stare J, Mavri J, Vianello R. Hydride Abstraction as the Rate-Limiting Step of the Irreversible Inhibition of Monoamine Oxidase B by Rasagiline and Selegiline: A Computational Empirical Valence Bond Study. Int J Mol Sci. 2020. — Computational/mechanistic study, rasagiline and selegiline both named directly, PMID 32858935. Shared with the equivalent entry in this project's Selegiline dossier (B009); see Overlap map.
  5. Naoi M, Maruyama W, Youdim MBH, et al. Molecular mechanism underlying neuroprotection by rasagiline. J Neurochem. 2002;81(s1):4. — Mechanistic study abstract, SH-SY5Y cells, rasagiline named directly, DOI 10.1046/j.1471-4159.2002.00012.x Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, authors, and a reconstructed abstract); the publisher's own page was not separately opened. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, authors, and a reconstructed abstract); the publisher's own page was not separately opened. PMID not independently confirmed in this review.
  6. Naoi M, Maruyama W, Youdim MBH, et al. Molecular Basis of Neuroprotective Activities of Rasagiline and the Anti-Alzheimer Drug TV3326. Cell Mol Neurobiol. 2001;21(6):555-573. — Mechanistic review, rasagiline named directly, PMID 12043833
  7. Maruyama W, Yamamoto T, Kitani K, Carrillo MC, Youdim MBH, Naoi M. Mechanism underlying anti-apoptotic activity of a (-)deprenyl-related propargylamine, rasagiline. Mech Ageing Dev. 2000;116(2-3):181-191. — Mechanistic study, rasagiline named directly, PMID 10996018
  8. Bar-Am O, Weinreb O, Amit T, Youdim MBH. The neuroprotective mechanism of 1-(R)-aminoindan, the major metabolite of the anti-parkinsonian drug rasagiline. J Neurochem. 2009;112(5):1131-1137. — Mechanistic review, rasagiline's active metabolite, DOI 10.1111/j.1471-4159.2009.06542.x Access note: confirmed via an OpenAlex single-record lookup by DOI; the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI; the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.
  9. Naoi M, Maruyama W, Yi H. Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria. J Neural Transm (Vienna). 2013;120(11):1539-1551. — Mechanistic study, SH-SY5Y cells, rasagiline named directly, DOI 10.1007/s00702-013-1033-x Access note: confirmed via an OpenAlex single-record lookup by DOI; the Springer publisher page itself was not separately opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI; the Springer publisher page itself was not separately opened in full. PMID not independently confirmed in this review.
  10. Lecht S, et al. (Lazarovici P, senior/corresponding author). Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling. Biomedicines. 2024;12(7):1592. — PC12 cell model, rasagiline (3-10 microM) tested directly, PMID 39062165, DOI 10.3390/biomedicines12071592
  11. Liu C, Zhang XL, Zhou L, Wang T, Quan Z, Zhang Y, Li J, Li GW, Zheng LF, Li LS, Zhu JX. Rasagiline, an inhibitor of MAO-B, decreases colonic motility through elevating colonic dopamine content. Neurogastroenterol Motil. 2018. — Rat model, rasagiline named directly, DOI 10.1111/nmo.13390 Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, full author list, and a reconstructed abstract); the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.Access note: confirmed via an OpenAlex single-record lookup by DOI (title, year, venue, full author list, and a reconstructed abstract); the Wiley publisher page itself returned an HTTP 403 error on direct fetch and was not opened in full. PMID not independently confirmed in this review.
  12. Zheng H, Fridkin M, Youdim MBH. Site-Activated Chelators Derived from Anti-Parkinson Drug Rasagiline as a Potential Safer and More Effective Approach to the Treatment of Alzheimer's Disease. Neurochem Res. 2010. — New hybrid prochelator compounds (HLA20A, M30D), DOI 10.1007/s11064-010-0293-1 Cohort note: the chelator compounds described are new molecules built using rasagiline's chemical scaffold as a design template, not rasagiline itself; fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.Cohort note: the chelator compounds described are new molecules built using rasagiline's chemical scaffold as a design template, not rasagiline itself; fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.
  13. Bar-Am O, Amit T, Kupershmidt L, et al. Neuroprotective and neurorestorative activities of a novel iron chelator-brain selective monoamine oxidase-A/monoamine oxidase-B inhibitor in animal models of Parkinson's disease and aging. Neurobiol Aging. 2015. — New compound VAR10303, DOI 10.1016/j.neurobiolaging.2014.10.026 Cohort note: VAR10303 is a new molecule chemically hybridizing rasagiline's N-propargyl moiety with a separate iron-chelating pharmacophore; not rasagiline itself, fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.Cohort note: VAR10303 is a new molecule chemically hybridizing rasagiline's N-propargyl moiety with a separate iron-chelating pharmacophore; not rasagiline itself, fails the Hard Rule 6 cohort test. Cited only under Iron to show this literature exists and was opened and screened, not as drug-specific supporting evidence.
  14. Mandel SA, Weinreb O, Amit T, Youdim MBH. Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. Brain Res Rev. 2005;48(2):379-387. — Review, DOI 10.1016/j.brainresrev.2004.12.027. Identified during the 2026-10-02 repair pass as a candidate Iron-entry source; its OpenAlex metadata record flags "iron chelation" as an indexed topic Access note: only the OpenAlex metadata record (title, authors, year, venue) could be opened; the full text is behind an Elsevier paywall (linkinghub.elsevier.com redirect) and could not be read, so whether its iron-chelation content applies to rasagiline itself or only to its derivatives could not be verified. Not relied upon as supporting evidence per the rule against citing an unopened source; listed to disclose the lead for a future revision.Access note: only the OpenAlex metadata record (title, authors, year, venue) could be opened; the full text is behind an Elsevier paywall (linkinghub.elsevier.com redirect) and could not be read, so whether its iron-chelation content applies to rasagiline itself or only to its derivatives could not be verified. Not relied upon as supporting evidence per the rule against citing an unopened source; listed to disclose the lead for a future revision.
  15. [Authors not individually broken out in the reconstructed metadata]. Features of Plasma Homocysteine, Vitamin B12, and Folate in Parkinson's Disease: An Updated Meta-Analysis. J Integr Neurosci. 2023;22(5). — Meta-analysis, Parkinson's disease patients on "dopaminergic medications" broadly (not broken out by MAO-B inhibitor vs. levodopa vs. COMT inhibitor); fails the Hard Rule 6 cohort test for rasagiline specifically. PMID 37735121. Cited only under Fails verification to source the real, disease-level finding being rebutted for rasagiline specifically.