Cyclazodone

Chemical identity

Identity here is unambiguous. The names are the moving part. One PubChem record covers cyclazodone: CID 135438121, CAS 14461-91-7, molecular formula C12H12N2O2, molecular weight 216.24, InChIKey DNRKTAYPGADPGW-UHFFFAOYSA-N, UNII O8U55ZRL9K. That record's IUPAC name is 2-cyclopropylimino-5-phenyl-1,3-oxazolidin-4-one. Most secondary pages write the tautomer instead, 2-(cyclopropylamino)-5-phenyl-1,3-oxazol-4(5H)-one, which sits in the same synonym list and denotes the same structure. The World Health Organization issued cyclazodone as an International Nonproprietary Name under INN number 2173, together with a French Denomination Commune Francaise. The same synonym list holds the development code LD 3695 and the descriptive name cyclopropylpemoline, and it is under that last name that the compound is indexed in the only journal paper that measured anything about it.

Four molecules share the 5-phenyl-1,3-oxazol-4(5H)-one core and differ only in what hangs off the 2-amino nitrogen. Pemoline carries an unsubstituted amino group. Thozalinone, PubChem CID 12602, carries a dimethylamino group. Fenozolone, CID 135436543, formula C11H12N2O2, carries an ethylamino group. Cyclazodone carries a cyclopropylamino group. A fifth, N-methylcyclazodone, adds a methyl to that same nitrogen: PubChem CID 156614124, C13H14N2O2, molecular weight 230.26, CAS 14461-92-8, UNII XRL7YKY7UX, development code LD 4202. The hyphenated spelling used in the literature does not resolve in PubChem's name index; the unhyphenated form does. The distinction matters, because the recent analytical literature is about the N-methyl compound rather than this one.

Physical characterisation comes from the originating patent and has not been independently republished. That document describes a white crystalline solid melting at 139 to 140 degrees Celsius, soluble in cold ethanol, insoluble in water, stable in alkaline medium and unstable in acid. A suspension in boiling ten per cent aqueous sulphuric acid was reported to convert rapidly to 5-phenyloxazolidine-2,4-dione. The elemental analysis printed alongside those observations agrees with C12H12N2O2 at a molecular weight of 216, matching the PubChem record.

The patent holds nearly all of the pharmacology

United States patent 3,609,159, titled 5-phenyl-2-cyclopropylamino-4-oxazolinone and process for making the same, was filed on 21 July 1967 and granted on 28 September 1971 to Les Laboratoires Dausse of Paris, naming Guidicelli and Najer as inventors. It is a continuation-in-part of two abandoned United States applications from 1964 and 1966 and claims three French priority dates in March and September 1963. A British equivalent, GB 1,005,738, bearing the same title, published on 29 September 1965. These documents, not the journal literature, are where the animal findings sit.

The motor-activity experiment is stated plainly. Mice were injected intraperitoneally with 0.01 grams per kilogram of the compound and compared with three other members of the series given by the same route at higher doses: the monomethylamino and dimethylamino congeners at 0.05 grams per kilogram, and the monoethylamino congener at both 0.01 and 0.05 grams per kilogram. Those comparator doses are stated in the description text even though the table cells are illegible. The tabulated result for cyclazodone gives a duration of maximum motive activity of 120 to 180 minutes and a total duration of excitation of six hours. Group sizes are not given for that table. The comparator rows are partly illegible in the scanned copy served by the patent databases, so only the cyclazodone row can be read with confidence.

A reserpine-antagonism experiment follows. Two lots of ten mice were used, one given the compound orally at 0.010 grams per kilogram and one given dl-amphetamine at the same oral dose; a third lot served as control, and the patent does not state its size. Two hours later all three lots received reserpine at 0.002 grams per kilogram intraperitoneally, and ptosis was scored at one, three and eighteen hours. The legible cells record ptosis in eight of ten and then seven of ten animals in the cyclazodone lot against ten of ten in both the amphetamine and control lots; the remaining cells and the table footnote are illegible in the scan. The patent's own conclusion is that the compound opposed reserpine at least as well as dl-amphetamine did.

Anorexia was tested separately in rats by the method of Roszkowski and colleagues. The patent reports an ED50 of 3.1 milligrams per kilogram for cyclazodone against 2.6 milligrams per kilogram for d-amphetamine, states neither the number of animals nor the route, and calls the two figures very similar. Lethal doses are given for cyclazodone as 0.081 grams per kilogram intraperitoneally and 0.142 grams per kilogram subcutaneously, against 0.340 grams per kilogram subcutaneously for the ethylamino congener. None of this was peer reviewed. A patent is a legal instrument written to support a claim of novelty, and its pharmacology sections are selected accordingly.

One journal paper, indexed without an abstract

Segal, Cox, Stern and Maickel published a six-page note in Life Sciences in December 1967 under the title Stimulatory effects of pemoline and cyclopropylpemoline on continuous avoidance behavior: similarity to effects of D-amphetamine. PubMed carries the record as PMID 6080576, at volume 6, issue 23, pages 2567 to 2572. No abstract is indexed, in PubMed, in Crossref or through the Semantic Scholar API, and the publisher's page returns HTTP 403. The MEDLINE indexing terms give what the record otherwise withholds: Rats, Male, Injections Intraperitoneal, Avoidance Learning drug effects, and the chemical list Amphetamine, Pemoline, Oxazoles and Pargyline.

Doses, group sizes, schedule parameters and effect magnitudes are therefore not retrievable from any indexed source. What can be stated is the design category, the species, the sex, the route and the fact that a monoamine oxidase inhibitor was among the substances the paper handled. The title asserts similarity to d-amphetamine on a continuous avoidance schedule; the measurement behind that assertion is not in the public record.

That paper has been cited four times in fifty-nine years, according to the Semantic Scholar citation graph: by a 1971 rat study of a different nootropic, by a 1973 book chapter on amphetamine-like drugs, by a 1992 microdialysis study, and by the 2008 review discussed below. A PubMed search for cyclazodone returns two records in total, and this note is neither of them: the two are the 2026 toxicokinetic paper and a 2017 instrument-methods paper. The 1967 note is indexed under the name cyclopropylpemoline instead, and a search for that name returns it alone.

The modern literature measures detection, not effect

Work published on this molecule since 2017 is analytical chemistry. Jeong and colleagues, at a doping-control laboratory in Seoul, used gas chromatography coupled to electrospray ionisation mass spectrometry to perform in-source hydrogen and deuterium exchange on eleven stimulants bearing secondary amino or hydroxyl groups. Corrected relative abundances of fully exchanged ions across the panel ran from 24.3 to 85.5 per cent, with etamivan excepted. Cyclazodone, along with methylephedrine, showed low exchange efficiency under acidic, neutral and basic spray-solvent conditions. The finding concerns the behaviour of a gas-phase ion.

Roiffe and colleagues validated a liquid chromatography Orbitrap method for adulterants in whey protein supplements and included cyclazodone in the analyte panel, reporting a retention time of 4.04 minutes, precursor mass 217.09715, extraction yield 87.3 per cent, repeatability 7.37 per cent and a limit of detection of 12.5 nanograms per gram in that matrix. Eleven commercial products were then screened. Seven proved adulterated, but the substances found were conivaptan, polythiazide and benfluorex. Cyclazodone was not detected in any sample.

Gampfer and colleagues published toxicokinetic work in 2026, and its subject is the N-methyl analogue rather than cyclazodone. Using pooled human liver S9 fraction, cDNA-expressed cytochromes and urine from male Wistar rats given a single oral dose of 2 milligrams per kilogram, they identified exactly one phase I metabolite of N-methyl-cyclazodone and no phase II metabolites. That metabolite is cyclazodone itself, formed by N-demethylation, catalysed predominantly by CYP2A6 at 57 per cent of hepatic net clearance at low substrate concentration, with CYP1A2 at 28 per cent and CYP2C19 at 15 per cent. Plasma protein binding of the N-methyl compound, measured by ultrafiltration in triplicate, was 36 plus or minus 5 per cent.

One consequence is worth stating precisely. In that rat model, neither the administered N-methyl compound nor its metabolite was detectable by gas chromatography mass spectrometry screening; using high-resolution liquid chromatography screening, the only substance found was cyclazodone. Detection of cyclazodone in a urine sample is therefore not by itself evidence of what was taken.

Mechanism claims and the citations attached to them

Five peer-reviewed papers mention this compound and none of them measured it. Docherty's 2008 survey of stimulants prohibited by the World Anti-Doping Agency lists cyclazodone in a table headed Stimulants prohibited in competition and sourced there to the 2007 WADA List, and explains the entry in one sentence: cyclopropylpemoline is not listed in the Martindale edition consulted, and it is a derivative of pemoline, which has stimulant actions similar to the effects of dexamphetamine. That last comparison carries a citation to Segal 1967, so the review anchors it to the one behavioural paper rather than to structure alone. Paiva and colleagues' 2024 review of supplement adulteration mentions cyclazodone only as an entry in the analyte panel of Roiffe 2019, and reports no measurement of its own.

Dhingra, Kaur and Ram's 2019 review of ocular effects of illicit drugs goes further. The review asserted, in a single sentence carrying one citation, that the compound produced stimulant and focus-enhancing effects comparable to dexamphetamine by increasing dopamine, noradrenaline and serotonin release, and that pupillary dilatation and altered brightness perception occurred at higher doses. No study, species, route or sample size was given for any part of that assertion. The citation attached to the passage is reference 77, which resolves to Baggott and colleagues 2011 in Drug and Alcohol Dependence: a web-based questionnaire on persisting visual phenomena in 2,455 analysed respondents with histories of hallucinogen use. That paper concerns lysergic acid diethylamide and related compounds and does not mention cyclazodone.

Napoletano and colleagues, cataloguing cognitive enhancers found by an automated web-crawling tool in 2020, reproduce the online marketing description of the N-methyl analogue verbatim, including the assertion that it is an approximately three- to fivefold more potent derivative of pemoline. The provenance of that phrasing is a vendor description harvested by the crawler, which is what the paper set out to catalogue; it acquires the appearance of a pharmacological finding only when quoted onward. No monoamine release, uptake or receptor-binding measurement for cyclazodone was located in PubMed, Europe PMC, the Guide to Pharmacology ligand database or ChEMBL.

Regulatory and anti-doping position

Cyclazodone holds no marketing approval anywhere. The National Center for Advancing Translational Sciences drug record for UNII O8U55ZRL9K classes it as investigational with no approval year. ChEMBL carries the molecule as CHEMBL2106536 with a maximum-phase field of 2, but the same record holds no indication entry, no mechanism-of-action entry and no bioactivity measurements at all, and the record does not state where the phase assignment came from.

The compound is not named in the DEA list of controlled substances in alphabetical order dated 12 August 2026. Pemoline is, at code 1530, Schedule IV, trade name Cylert. Pemoline itself was taken off the United States market in October 2005 over hepatic failure reports, and the Food and Drug Administration formally withdrew approval of new drug applications 016832 and 017703 on 23 May 2023 at Abbott's request, published at 88 FR 33148. Those events belong to pemoline's record. No liver-injury study of cyclazodone in any species was located.

Anti-doping status is misstated in both directions. Cyclazodone was expressly named among the stimulants prohibited in competition on the WADA List Docherty reproduced in 2008, sourced there to WADA 2007. It is not named on the 2026 List, which was verified by extracting the text; the delisting, not the original claim, is what current statements miss. The 2026 List mentions cyclazodone in neither its text nor its index; pemoline appears in S6.A among the non-specified stimulants. Section S6 is prohibited in competition and closes with the catch-all and other substances with a similar chemical structure or similar biological effect(s), which is the mechanism by which unlisted stimulants are captured. Whether such a substance is Specified follows from Code Article 4.2.2, quoted in the List's introduction, not from S6 itself. Pokrywka and colleagues, surveying the Polish supplement market in 2025, placed cyclazodone in the category of unclear status presumed to meet WADA criteria, cross-referenced to pemoline.

What is not known

No human study of cyclazodone exists in any retrievable form. ClinicalTrials.gov intervention and term searches for cyclazodone, cyclopropylpemoline and N-methylcyclazodone each returned zero registered studies, so there is no dose-ranging, pharmacokinetic, safety or efficacy work in people to report. No case report of intoxication attributed to cyclazodone itself is indexed. The one presumed intoxication case in this chemical space, referred to by Gampfer 2026 as the first United States report of N-methyl-cyclazodone in 2022, concerns the N-methyl analogue rather than this compound, and cyclazodone's status as that analogue's sole metabolite means the two cannot be separated by a urine finding. Nothing is known about absorption, distribution, half-life, clearance or excretion in any species: no pharmacokinetic parameter of any kind was located. The molecular target is unidentified. No binding assay, no uptake assay and no release assay has been published for this compound at any monoamine transporter or receptor, and ChEMBL holds no bioactivity record for it, so every mechanistic statement in circulation rests on structural analogy to pemoline rather than on measurement. Repeated administration has not been examined in any species: no tolerance, dependence, withdrawal, receptor-regulation, reproductive, developmental or carcinogenicity study was found. Liver toxicity, the reason its parent compound was withdrawn from the United States market, has never been tested on it. The animal record that does exist consists of one 1967 rat paper indexed without an abstract and a 1971 patent whose tables give no group sizes for most experiments and whose scanned text is partly illegible. Whether material sold under this name is the compound described here is a separate question that no published survey has addressed; the one supplement-screening study that included cyclazodone in its analyte panel did not detect it in any product tested.

Questions