Cyclazodone

N-cyclopropyl pemoline

Cyclazodone (N-cyclopropyl pemoline) is a cognitive & mood research compound. A pemoline derivative — dopaminergic and noradrenergic releasing agent with a long duration and a slow onset that makes redosing tempting.

How Cyclazodone works

A pemoline derivative — dopaminergic and noradrenergic releasing agent with a long duration and a slow onset that makes redosing tempting.

Proposed benefits

Researched for focus, memory, neuroprotection, mood and stress resilience.

Where to get Cyclazodone

The evidence for Cyclazodone

Graded by what exists behind each claim.

Human clinical evidence

• No human trials: development stopped at preclinical, so the ceiling on any claim here is a rodent model — and these transfer poorly.

📊 Correlative data

• Community use as a stimulant. Reported experience is of strong, long-lasting focus with appetite suppression and difficulty sleeping — a conventional stimulant profile.
• There is no human safety data whatsoever, which for a compound with cardiovascular-relevant stimulant activity is a more serious gap than it is for most things here.

🧪 How the mechanism reads

• An N-cyclopropyl derivative of pemoline, a discontinued stimulant. It is believed to act on dopamine and noradrenaline as a releasing agent or reuptake inhibitor.
• Pemoline itself was withdrawn for hepatotoxicity — idiosyncratic liver failure — and no one has established whether the cyclopropyl derivative shares that liability. That is the single most important thing about it and it is unresolved.

Why an empty tier is not a verdict →

How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →

What Cyclazodone actually does

Get the structure right first, because the risk argument is entirely structural. Pemoline is 2-amino-5-phenyl-1,3-oxazol-4(5H)-one, C9H8N2O2, 176.17 Da — a five-membered oxazolidinone ring with a phenyl at C5 and an exocyclic amino group at C2. Cyclazodone is the same ring with a cyclopropyl group on that C2 nitrogen: C12H12N2O2, 216.24 Da. One substituent, 40 Da, and no other change.

Why a cyclopropylamine is not a neutral decoration. N-cyclopropylamines are a textbook mechanism-based inactivator motif for cytochrome P450 and for monoamine oxidase. The chemistry is specific: the enzyme abstracts a single electron from the amine nitrogen, the resulting aminium radical cation triggers ring-opening of the strained cyclopropane, and the primary carbon radical that appears alkylates whatever is nearest — the heme, or an active-site residue. That is how tranylcypromine-class and several cyclopropylamine P450 inhibitors work by design. Nobody has tested whether it happens with cyclazodone. It is an extrapolation from the motif and it is flagged as one — but it is the specific reason that assuming a cyclopropyl analog of a hepatotoxic drug is safer than its parent has the chemistry pointing the other way.

The one piece of real metabolic data, and it arrives sideways. Gampfer 2026 characterized N-methyl-cyclazodone — a different analog, methylated rather than cyclopropylated — in pooled human liver S9 fraction and in rat urine by HPLC high-resolution tandem mass spectrometry. One phase I metabolite was identified, formed by N-demethylation, and metabolism was primarily mediated by CYP2A6; plasma protein binding was low to moderate, so protein-binding displacement interactions are unlikely; and the authors state that drug-drug interactions on polydrug use cannot be excluded when co-ingested with other substrates of the same isoforms Gampfer 2026. Note what N-demethylation of N-methyl-cyclazodone produces: by definition, cyclazodone. So the closest thing to human metabolic data this compound has is a study in which it appears as somebody else's metabolite.

Why CYP2A6 is the interesting answer. CYP2A6 is among the most polymorphic human cytochromes: whole-gene deletion alleles are common in East Asian populations and rare in Europeans, and it is the principal enzyme clearing nicotine, which is why slow-nicotine-metabolizer status is a real and measurable phenotype. If cyclazodone's own N-dealkylation runs through the same enzyme as its N-methyl sibling's — an extrapolation, not a finding — then the ‘12+ hours’ duration people quote is a population average concealing a genetically determined spread, and the same milligram dose is a different drug in two different people.

Pharmacodynamics: there are none published. Cyclazodone is described as a dopaminergic and noradrenergic releasing agent or reuptake inhibitor. No binding affinity, no uptake inhibition constant, no functional assay for this molecule at DAT, NET, SERT, TAAR1 or any receptor has appeared in the literature. The description is inherited from pemoline and from what people report feeling.

Cell, rodent, human — and where it stops

Step one, in a tube — and it is the wrong molecule. Pooled human liver S9 fraction, CYP reaction phenotyping and plasma protein binding, on N-methyl-cyclazodone Gampfer 2026. Cyclazodone itself has never been through a microsomal or S9 incubation in the published literature.

Step two, in rodents — also the wrong molecule. Rat urine metabolite profiling by HPLC-HRMS/MS, again on N-methyl-cyclazodone Gampfer 2026. There is no rodent pharmacology, no rodent toxicology and no rodent behavioral study for cyclazodone.

Step three, in humans: zero, for this compound. No pharmacokinetics, no controlled exposure, no dose-finding, no adverse-event registry. The compound reaches readers through the research-chemical market, which is itself the subject of the literature that does exist: reviews of the online cognitive-enhancer market Napoletano 2020 and a market surveillance study run by 12 official medicines control laboratories across Europe and Australia, which documented 159 samples, 166 identifications and 34 distinct molecules between January 2020 and September 2024, 69% of them from the illegal market Vanhee 2025.

What people actually reason from, and why neither half transfers. The argument in every forum is: pemoline killed people, therefore this is dangerous; or, pemoline was withdrawn for an idiosyncratic reaction, therefore this is fine. Look at what the parent's own numbers do. Berkovitch, working from a single new case of fulminant liver failure in a 14-year-old and the two previously published fatal cases, calculated a relative risk of fulminant liver failure on pemoline of 45.3, with a 95% confidence interval of 4.1 to 510 Berkovitch 1995. Two years later a descriptive meta-analysis of the literature and drug-reporting databases concluded that current assumptions about the risk of acute hepatic failure from pemoline alone were overestimates Shevell 1997. So the parent drug's risk is quantified to within a 124-fold interval and the direction of the correction is disputed.

The obstacles, and they are unusually clean. (1) Transporting a number with a 4.1-to-510 confidence interval onto a different molecule is not a risk estimate. It is a mood, and both the alarmed and the relaxed versions of it are equally unsupported. (2) The only metabolic data is on the wrong analog, and the difference is the part that matters. An N-methyl group leaves by ordinary N-demethylation Gampfer 2026; an N-cyclopropyl group, if it leaves at all, does so through a ring-opening that generates a reactive intermediate. Those are not variations on a theme; they are the difference between a clean clearance route and a bioactivation route. (3) The dose has no derivation. Pemoline was prescribed at 37.5–112.5 mg/day; cyclazodone is sold at 10–30 mg with no potency comparison ever having been made between them, in any species. The ratio came from the market. (4) The reported duration is a self-report. ‘12+ hours’ describes when people stop noticing it, which is not a half-life and, for a stimulant with acute tolerance, may arrive long before the drug has gone.

Cyclazodone pharmacokinetics — how much of it actually gets in

The catalog says ‘Long; commonly reported as 12+ hours’. There is no human pharmacokinetic measurement for this molecule, so what follows is a bound and a set of inferences, labeled as such.

What degrades it, as far as anyone knows. The nearest measurement is on N-methyl-cyclazodone: primarily CYP2A6, one phase I metabolite by N-dealkylation, low-to-moderate plasma protein binding Gampfer 2026. For cyclazodone the same oxidative N-dealkylation is the obvious route, and the extrapolation carries a caveat that ordinary dealkylations do not: cleaving a cyclopropylamine proceeds through a ring-opened carbon radical, which is a reactive species rather than a stable metabolite. The oxazolidinone ring itself is also hydrolytically openable, which would give a phenylglycine-type fragment. None of this has been measured for this compound.

The oral barrier. 216.24 Da, neutral at physiological pH, one aromatic ring and one small heterocycle: this is a molecule with no absorption problem. There is no ionized group to trap it in the lumen, no peptide bond for brush-border peptidases, no ester for gut esterases, and nothing published suggesting it is a P-glycoprotein substrate. High passive permeability is the expectation, and the corollary is that the entire dose-to-exposure relationship is set by hepatic clearance rather than by absorption — which is exactly the step CYP2A6 polymorphism would make variable.

The number that is missing and the one that is not. Missing: a single plasma concentration in a single human, ever. Not missing: the dose people take, 10–30 mg, against a parent drug prescribed at 37.5–112.5 mg/day. Those two figures are the whole quantitative basis of this compound's use, and one of them belongs to a different molecule.

Route. Oral only. Nothing else has been studied, and the absence of any absorption, distribution or excretion data means there is no basis whatever for assuming a nasal or sublingual route would behave proportionally.

What would have to be true, and how you would know it was not

Four predictions. The first is the one most likely to be misread, so it goes first and it argues against a habit rather than against the drug.

1. Against the monitoring plan: a normal CMP will not warn you. The hepatotoxicity that ended pemoline was idiosyncratic — not dose-proportional, not preceded by a reliable slow transaminase drift, which is precisely why the periodic liver-function testing mandated on its US label did not prevent the fatal cases Berkovitch 1995 Shevell 1997. Prediction: a comprehensive metabolic panel and a GGT drawn at 6 weeks on cyclazodone come back normal in essentially everyone, and that normality has almost no negative predictive value for the event people are worried about. There is no retest window that fixes this, and saying so is more useful than inventing one.

2. Resting heart rate will rise, and a wearable already measures it. A dopaminergic and noradrenergic releasing agent raises resting heart rate and blood pressure. Take the seven-day average resting heart rate from the week before use and the week of use. Prediction: a rise of roughly 5–10 bpm at 10–30 mg, and a systolic blood pressure rise measurable on a home cuff at 2–4 hours post-dose. If neither moves at all, the compound is either underdosed or not what the label says — and given that 75% of declared quantities in this product category were inaccurate Cohen 2021, that is a live possibility rather than a rhetorical one.

3. Actigraphy tests the duration claim, which nothing else does. ‘12+ hours’ is a subjective report. Wear a sleep tracker; compare total sleep time and sleep onset latency on a morning-dosed day against matched non-dosed days. Prediction: if the reported duration is real, a morning dose measurably delays sleep onset the same night. If it does not, the duration figure describes psychological expectation rather than pharmacology, and the whole ‘it lasts so long that redosing is tempting’ framing needs revisiting.

4. CYP2A6 status should predict duration, and it is on consumer panels. If cyclazodone shares the clearance route of its N-methyl analog Gampfer 2026, then a person carrying a reduced-function or deleted CYP2A6 allele should experience a markedly longer effect from the same milligram dose — and someone taking anything that inhibits CYP2A6 alongside it should too. This is the most falsifiable pharmacogenomic prediction on this page, it is extrapolated rather than measured, and nobody has ever collected the data that would test it.

What nobody has tested yet

Five experiments. The fourth is the one that ought to exist before anybody sells this.

1. No human plasma concentration has ever been published. Not one, at any dose. Every statement about this compound's onset, peak and duration comes from people describing how they felt. A six-person, single-dose, eight-timepoint LC-MS study would create the compound's entire pharmacokinetic literature in a day.

2. Nobody has put cyclazodone itself through liver S9. The protocol already exists and has already been run — on the N-methyl analog Gampfer 2026. The same laboratory, the same incubation, the same instrument, with the cyclopropyl compound in the tube, would answer whether the cyclopropylamine opens and which cytochrome does it. It is a direct extension of published work and it has not been done.

3. There is no monoamine transporter panel. DAT, NET and SERT binding and uptake inhibition constants are a routine commercial assay. For a compound sold and taken as a stimulant, the basic pharmacology — which transporter, releaser or blocker, what potency — has never been measured.

4. Nobody has run a reactive-metabolite trapping study. Incubate the compound in human liver microsomes with glutathione or potassium cyanide as a trap and look for adducts by mass spectrometry. That is the standard screen for the kind of bioactivation implicated in idiosyncratic liver injury, it is a one-week experiment, and it is the single most decision-relevant unrun study for a cyclopropylamine analog of a drug withdrawn for hepatic failure Berkovitch 1995.

5. Nobody has sampled the market for this compound specifically. Twelve national medicines control laboratories surveyed 159 nootropic samples and 34 molecules over four years Vanhee 2025, and cyclazodone's own supply chain — identity, purity, and whether what is sold is cyclazodone or the N-methyl analog that has actually been characterized — has never been sampled at all.

Cyclazodone — its own safety story, not its class's

The class block is generic to stimulants. Five things here are this molecule's own, and the honest summary is that the risk is unquantified rather than known to be high or low.

1. The parent's number, with its uncertainty attached. Relative risk of fulminant liver failure on pemoline: 45.3 (95% CI 4.1–510), computed from three fatal cases Berkovitch 1995; a subsequent critical analysis of the same literature and the drug-reporting databases concluded that risk assumptions of that kind were overestimates and offered monitoring recommendations instead Shevell 1997. Pemoline left the US market in 2005. Both papers are cited here so a reader can see that the field disagreed with itself, which is more informative than either number alone.

2. The structural reason the derivative is not automatically safer. N-cyclopropylamine is a mechanism-based inactivation motif whose oxidation opens the ring to a reactive radical. Cyclazodone carries one; pemoline does not. This is an extrapolation from medicinal chemistry rather than a measurement on this compound, and it points the opposite way to the common assumption that the newer analog is the cleaner one.

3. The interaction axis is CYP2A6, not the usual suspects. The closest analog is cleared primarily by CYP2A6 with low-to-moderate protein binding, and the authors explicitly flag polydrug drug-drug interactions with other substrates of the same isoform Gampfer 2026. That is a different list from the CYP3A4 and CYP2D6 interactions people usually check, and CYP2A6 has common null alleles — so both ‘what else are you taking’ and ‘who are you’ change the exposure.

4. Monitoring gives false comfort, which is a harm of its own. A clean liver panel is often read as permission to continue. For an idiosyncratic hepatic reaction it is nothing of the kind, and a person who would otherwise have used the compound cautiously and briefly may use it longer because a number came back normal.

5. Count the human data: zero. No trial arm has ever existed in which an adverse event could have been recorded for cyclazodone, so ‘no reported problems’ is not a safety finding. Combine that with 75% inaccurate label quantities and up to four-fold overdelivery in this product category Cohen 2021 and a market surveillance record showing most samples come from illegal supply Vanhee 2025, and the position is that the dose is unverified, the molecule is uncharacterized, and the parent drug killed people. That is not a reason for panic and it is not a reason for comfort; it is the reason this compound is listed with a warning rather than a protocol.

Sources read for this page

• Gampfer TM, Klaes S, Eckstein N, Meyer MR. Toxicokinetic Studies of the Two Stimulants M-ALPHA and N-Methyl-cyclazodone Using In Vitro and In Vivo Tools. Metabolites 2026;16(5):291 · PMID 42188000
• Berkovitch M, Pope E, Phillips J, Koren G. Pemoline-associated fulminant liver failure: testing the evidence for causation. Clinical Pharmacology and Therapeutics 1995;57(6):696-698 · PMID 7781270
• Shevell M, Schreiber R. Pemoline-associated hepatic failure: a critical analysis of the literature. Pediatric Neurology 1997;16(1):14-16 · PMID 9044395
• Napoletano F, Schifano F, Corkery JM, Guirguis A, Arillotta D, Zangani C, Vento A. The Psychonauts' World of Cognitive Enhancers. Frontiers in Psychiatry 2020;11:546796 · PMID 33024436
• Vanhee C, Deconinck E, George M, Hansen A, Hackl A, Wollein U, El-Atma O, Beerbaum N, Aureli F, Borioni A, et al. The Occurrence of Illicit Smart Drugs or Nootropics in Europe and Australia and Their Associated Dangers: Results from a Market Surveillance Study by 12 Official Medicines Control Laboratories. Journal of Xenobiotics 2025;15(3):88 · PMID 40558871
• Cohen PA, Avula B, Wang YH, Zakharevich I, Khan I. Five Unapproved Drugs Found in Cognitive Enhancement Supplements. Neurology: Clinical Practice 2021;11(3):e303-e307 · PMID 34484905

Cyclazodone — safety, predicted from mechanism

Cyclazodone — interference & stacking

Bloodwork to run alongside Cyclazodone

Baseline first, then again at 8–12 weeks.

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Cyclazodone — frequently asked questions

What Cyclazodone is used for

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