Unifiram (DM-232)

updated

Unifiram (DM-232) is a research compound sold for acute cognition enhancement and often used interchangeably with sunifiram (DM-235), which is a different molecule. Its published work is mouse and rat amnesia tests and rat brain-slice experiments, all from the group that discovered it, and no controlled human study exists: a PubMed query on 10 October 2026 found no record of unifiram given to a person. It has a stereocenter, so a vendor product may be a racemate.

Bicyclic lactam sulfonamide nootropic (AMPA mechanism indirect)

  • Unifiram is PubChem CID 9861054, C13H15FN2O3S, molecular weight 298.34, CAS 272786-64-8, a bicyclic lactam with a sulfonamide; sunifiram (DM-235) is a different molecule, CID 4223812, an acylpiperazine.
  • In the 2000 paper DM 232 was active at 0.001 mg/kg subcutaneously in mouse passive avoidance, and a 2006 review by the discovering group says unifiram and sunifiram are four orders of magnitude more potent than piracetam.
  • In mice DM 232 at 0.1 mg/kg intraperitoneally reversed amnesia caused by the AMPA antagonist NBQX, and in rat hippocampal slices it increased excitatory synaptic transmission; no abstract shows unifiram binding to AMPA receptors.
  • The (R)-(+) enantiomer of DM232 was more potent than the (S)-(-) enantiomer, producing comparable effects at 3-fold to 10-fold lower doses, and the PubChem name carries no stereodescriptor.
  • The isopropylsulfonyl analog of unifiram was amnesic, and two compounds in a related structure-activity series had amnesic activity nearly equipotent to scopolamine.
  • A PubMed query on 10 October 2026 returned 11 records, and none reports unifiram given to a person or any pharmacokinetic, toxicology or safety study.

What is unifiram, and what is its regulatory status?

Unifiram (DM-232) is a bicyclic lactam with a sulfonamide, PubChem CID 9861054, and a different molecule from sunifiram (DM-235). It has a stereocenter, so a vendor product may be a racemate, and it has no FDA label, no application and no registered study.

Unifiram is PubChem CID 9861054, C13H15FN2O3S, 298.34 g/mol, CAS 272786-64-8, 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, with DM 232 among the synonyms. It is a bicyclic lactam with a sulfonamide.

Sunifiram (DM-235) is a different molecule: CID 4223812, C14H18N2O2, 246.30 g/mol, an acylpiperazine. The two share a research group and a test system, not a structure, and no source in the records reviewed shows they are interchangeable in dose or effect; see the sunifiram page.

Unifiram has a stereocenter. The (R)-(+) and (S)-(-) enantiomers differ in potency, and the PubChem name carries no stereodescriptor, so a vendor product may be a racemate. A PubMed query on the DM 232 spelling also matches an unrelated German study of returned drugs, where DM 232,920 is a price in marks, so literature searches need the name. No public record ties any vendor material to the studied compound.

On 10 October 2026 ClinicalTrials.gov queries for unifiram and for DM232 or DM-232 returned no studies, DailyMed returned no label for unifiram, and an openFDA Drugs@FDA query returned no match. Status outside the United States is not covered here.

PubChem: unifiram identity, the stereocenter, and how it differs from sunifiram

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 9861054, 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one (unifiram, DM-232).

Unifiram is PubChem CID 9861054, C13H15FN2O3S, 298.34 g/mol, CAS 272786-64-8 (listed among the synonyms), IUPAC name 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, with DM 232 among the synonyms. It is a bicyclic lactam with a sulfonamide. Sunifiram (DM-235) is a different molecule (CID 4223812, C14H18N2O2, 246.30 g/mol, an acylpiperazine), so the two share a research group and a test system, not a structure, and no source in the records reviewed shows they are interchangeable in dose or effect. Unifiram has a stereocenter; the (R)-(+) and (S)-(-) enantiomers differ in potency, and the PubChem name carries no stereodescriptor, so a vendor product may be a racemate. A PubMed query on the 'DM 232' spelling also matches an unrelated German study of returned drugs ('DM 232,920' is a price in marks), so literature searches need the name.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule; racemate or enantiomers
Follow-up
Not applicable
Study design
Chemical database record; original reports
Funding
not stated in the source

Identity record only. No public record ties any vendor material to the studied compound.

Read the original source
Label and registry searches, 10 October 2026: no label, no match, no study

Regulatory record

U.S. Food and Drug Administration (DailyMed label search; openFDA Drugs@FDA query) and ClinicalTrials.gov. Searches for unifiram and for DM232 and DM-232, run 10 October 2026.

ClinicalTrials.gov queries for unifiram and for DM232 or DM-232 returned no studies, DailyMed returned no label for unifiram, and the openFDA Drugs@FDA query returned no match.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated label, application and registry search
Funding
not stated in the source

An absence finding as of 10 October 2026. It covers United States label, application and registry records only.

Read the original source

What did the mouse, rat and tissue studies find?

In mice unifiram was active in a passive avoidance test at 0.001 mg/kg subcutaneously and reversed amnesia caused by an AMPA antagonist, and in rat hippocampal slices it increased excitatory synaptic transmission. All of it is rodent and tissue work from the group that discovered it, rescue of induced deficits, and no controlled human study exists.

In the 2000 paper, 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones were tested in vivo in the mouse passive avoidance test and shown to be a new class of nootropic agents with a profile very similar to piracetam and much higher potency, and compound 7 (DM 232) was active at 0.001 mg/kg subcutaneously. The abstract does not name the amnesic challenge.

A 2006 review by the discovering group says unifiram and sunifiram are four orders of magnitude more potent than piracetam, prevent amnesia induced by modulation of several neurotransmission systems, increase acetylcholine release from rat cerebral cortex, and, for unifiram, increase the amplitude of field excitatory postsynaptic potentials in rat hippocampal slices. The potency comparison is against piracetam in mouse and rat amnesia tests, not against any approved cognitive drug in people.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner.

Everything here is reversal of an induced deficit in mice, rats or tissue, from one academic group. The newest unifiram pharmacology paper in the records reviewed is from 2005 to 2006, and no independent replication of unifiram itself was found; the 2013 independent work was on sunifiram.

2000 discovery paper: DM 232 active at 0.001 mg/kg subcutaneously in mouse passive avoidance

Animal study

Manetti D et al. J Med Chem. 2000;43(10):1969-74. PMID 10821709.

In the 2000 paper, 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones were tested in vivo in the mouse passive avoidance test and shown to be a new class of nootropic agents with a profile very similar to piracetam and much higher potency, and compound 7 (DM 232) was active at 0.001 mg/kg subcutaneously. The abstract does not name the amnesic challenge.

Participants / model
Mice
Treatment
Subcutaneous
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

From the group that discovered the compound.

Read the original source
Discoverers' 2006 summary: four orders of magnitude over piracetam, no receptor binding, AMPA hypothesis

Narrative review (preclinical literature)

Romanelli MN et al. CNS Drug Rev. 2006;12(1):39-52. PMID 16834757.

A 2006 review by the discovering group says unifiram and sunifiram are four orders of magnitude more potent than piracetam, show no affinity in binding studies for the most important central receptors or channels, prevent amnesia induced by modulation of several neurotransmission systems, increase acetylcholine release from rat cerebral cortex, and, for unifiram, increase the amplitude of field excitatory postsynaptic potentials in rat hippocampal slices; slice experiments support a role for AMPA receptors.

Participants / model
Mice, rats, rat cortical and hippocampal tissue
Treatment
Not stated in the review abstract
Follow-up
not stated in the source
Study design
Review by the discovering group
Funding
not stated in the source

The potency comparison is against piracetam in mouse and rat amnesia tests, not against any approved cognitive drug in people.

Read the original source
Mice: reversal of NBQX amnesia at 0.1 mg/kg; rat slices: increased synaptic transmission with unifiram

Animal study

Galeotti N et al. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(6):538-45. PMID 14600801.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner. No abstract shows unifiram binding to AMPA receptors. A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead (PMID 23733502), and no equivalent test of unifiram was found.

Participants / model
Mice; rat hippocampal slices
Treatment
Intraperitoneal in mice; tissue bath in slices
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect.

Read the original source
PubMed, 10 October 2026: 11 records, none gives unifiram to a person

PubMed search record

PubMed search run 10 October 2026: unifiram[tiab] OR DM-232[tiab] OR DM232[tiab] OR "DM 232"[tiab], with a follow-up query adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety.

The search returned 11 records and abstracts were read for all 11: 1 unrelated (the 2001 returned-drugs study), 6 chemistry or structure-activity papers, 1 pharmacology paper, the 2006 pharmacology review, and 2 market reviews. Adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety returned 5, none reporting unifiram given to a person. No unifiram pharmacokinetic, toxicology or safety study appears, and the newest unifiram pharmacology paper is from 2005 to 2006. No controlled human trial exists in the records reviewed.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source

How does unifiram act, and is it AMPA potentiation?

The proposed mechanism is AMPA receptor involvement, and the evidence is indirect: reversal of amnesia caused by an AMPA antagonist and increased synaptic transmission in rat slices. No abstract shows unifiram binding to AMPA receptors, binding studies found no affinity for the main central receptors or channels, and a 2013 independent paper attributes the related compound sunifiram to the NMDA glycine site.

A 2006 review by the discovering group says unifiram and sunifiram show no affinity in binding studies for the most important central receptors or channels, and that slice experiments support a role for AMPA receptors. Both increase acetylcholine release from rat cerebral cortex.

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect. DM 232 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX in mice, and in rat hippocampal slices it reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and increased excitatory synaptic transmission in a concentration-dependent manner.

A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead, and no equivalent test of unifiram was found, so the glycine-site finding is a competing proposal that has not been tried on unifiram.

Discoverers' 2006 summary: four orders of magnitude over piracetam, no receptor binding, AMPA hypothesis

Narrative review (preclinical literature)

Romanelli MN et al. CNS Drug Rev. 2006;12(1):39-52. PMID 16834757.

A 2006 review by the discovering group says unifiram and sunifiram are four orders of magnitude more potent than piracetam, show no affinity in binding studies for the most important central receptors or channels, prevent amnesia induced by modulation of several neurotransmission systems, increase acetylcholine release from rat cerebral cortex, and, for unifiram, increase the amplitude of field excitatory postsynaptic potentials in rat hippocampal slices; slice experiments support a role for AMPA receptors.

Participants / model
Mice, rats, rat cortical and hippocampal tissue
Treatment
Not stated in the review abstract
Follow-up
not stated in the source
Study design
Review by the discovering group
Funding
not stated in the source

The potency comparison is against piracetam in mouse and rat amnesia tests, not against any approved cognitive drug in people.

Read the original source
Mice: reversal of NBQX amnesia at 0.1 mg/kg; rat slices: increased synaptic transmission with unifiram

Animal study

Galeotti N et al. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(6):538-45. PMID 14600801.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner. No abstract shows unifiram binding to AMPA receptors. A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead (PMID 23733502), and no equivalent test of unifiram was found.

Participants / model
Mice; rat hippocampal slices
Treatment
Intraperitoneal in mice; tissue bath in slices
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect.

Read the original source

Do the two forms of unifiram differ, and can analogs be amnesic?

Yes to both. The (R)-(+) enantiomer was more potent than the (S)-(-) enantiomer, producing comparable effects at 3-fold to 10-fold lower doses, and the isopropylsulfonyl analog of unifiram and some related compounds were amnesic. A racemic product, or one containing a related compound, would not match the single compound studied.

The (R)-(+) enantiomer of DM232 was more potent than the (S)-(-) enantiomer in the passive avoidance and social learning tests and in acetylcholine release from rat cerebral cortex, producing comparable effects at 3-fold to 10-fold lower doses (enantiomeric excess above 99.9%). The PubChem name carries no stereodescriptor, so a vendor product may be a racemate.

The isopropylsulfonyl analog of unifiram was endowed with amnesic properties, and its two enantiomers had the same amnesic potency. A structure-activity study reports that none of the compounds made reached the potency of unifiram and sunifiram and that two (numbered 13 and 14) had amnesic activity nearly equipotent to scopolamine. Later series report that some cyclohexane derivatives induce amnesia, and 2- and 3-phenylpiperazines related to DM235 and DM232 were less potent than the parents in reversing scopolamine-induced amnesia in mouse passive avoidance.

The class is easy to push in either direction, and a product that contains a sulfonyl analog or a related piperazine would not be expected to behave as unifiram.

R-(+) more potent than S-(-) by 3-fold to 10-fold; the isopropylsulfonyl analog was amnesic

Animal study

Martini E et al. Med Chem. 2005;1(5):473-80. PMID 16787332.

The (R)-(+) enantiomer of DM232 was more potent than the (S)-(-) enantiomer in the passive avoidance and social learning tests and in acetylcholine release from rat cerebral cortex, producing comparable effects at 3-fold to 10-fold lower doses (enantiomeric excess above 99.9%). The isopropylsulfonyl analog of unifiram was endowed with amnesic properties, and its two enantiomers had the same amnesic potency.

Participants / model
Mice; rat cerebral cortex
Treatment
Not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A vendor product that is racemic, or that contains a sulfonyl analog, would not match the single compound studied.

Read the original source
Analog series: none matched the parents, two were amnesic, phenylpiperazines were less potent

Animal study

Scapecchi S et al. Bioorg Med Chem. 2004;12(1):71-85. PMID 14697772.

A structure-activity study reports that none of the compounds made reached the potency of unifiram and sunifiram and that two (numbered 13 and 14) had amnesic activity nearly equipotent to scopolamine. Later series made unifiram and sunifiram analogs with good antiamnestic activity and higher potency than piracetam, and reported that some cyclohexane derivatives induce amnesia (PMID 18954993). 2- and 3-phenylpiperazines related to DM235 and DM232 were less potent than the parents in reversing scopolamine-induced amnesia in mouse passive avoidance (PMID 25813160).

Participants / model
Mice
Treatment
Not stated in the abstracts
Follow-up
not stated in the source
Study design
Original chemistry and pharmacology studies
Funding
not stated in the source

The class is easy to push in either direction.

Read the original source
PubChem: unifiram identity, the stereocenter, and how it differs from sunifiram

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 9861054, 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one (unifiram, DM-232).

Unifiram is PubChem CID 9861054, C13H15FN2O3S, 298.34 g/mol, CAS 272786-64-8 (listed among the synonyms), IUPAC name 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, with DM 232 among the synonyms. It is a bicyclic lactam with a sulfonamide. Sunifiram (DM-235) is a different molecule (CID 4223812, C14H18N2O2, 246.30 g/mol, an acylpiperazine), so the two share a research group and a test system, not a structure, and no source in the records reviewed shows they are interchangeable in dose or effect. Unifiram has a stereocenter; the (R)-(+) and (S)-(-) enantiomers differ in potency, and the PubChem name carries no stereodescriptor, so a vendor product may be a racemate. A PubMed query on the 'DM 232' spelling also matches an unrelated German study of returned drugs ('DM 232,920' is a price in marks), so literature searches need the name.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule; racemate or enantiomers
Follow-up
Not applicable
Study design
Chemical database record; original reports
Funding
not stated in the source

Identity record only. No public record ties any vendor material to the studied compound.

Read the original source

Is unifiram an acute cognition enhancer, and is it interchangeable with sunifiram?

Only partly. Acute cognition is supported only as reversal of drug-induced amnesia in rodents, and used interchangeably with sunifiram is not supported: they are different molecules with different mechanism evidence, and no source compares them in people.

Sellers describe acute cognition enhancement and treat unifiram and sunifiram as interchangeable. The cognition part is supported only as reversal of drug-induced amnesia in mice and rats from one academic group. Interchangeability is not supported: the molecules differ in structure, the mechanism evidence differs (indirect AMPA evidence for unifiram, an NMDA glycine-site finding for sunifiram), and no source compares them in dose or effect.

The 2016 review by Gualtieri, who led the group that discovered the two molecules, says they were not protected by a patent and that about 12 years after their 2000 disclosure he found dozens of web sites offering them as drugs that improve cognition in healthy individuals, although only few preclinical studies were done and long-term toxicity was unknown. A 2022 review of smart drugs in healthy people names unifiram analogues among the popular cognitive enhancers and says efficacy in healthy individuals is uncertain and reported improvement temporary; its harm statements are for the enhancer classes together, not for unifiram.

A PubMed query on 10 October 2026 for unifiram, DM-232, DM232 and DM 232 returned 11 records, and abstracts were read for all 11. Adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety returned 5, and none reports unifiram given to a person. No controlled human trial exists in the records reviewed.

2000 discovery paper: DM 232 active at 0.001 mg/kg subcutaneously in mouse passive avoidance

Animal study

Manetti D et al. J Med Chem. 2000;43(10):1969-74. PMID 10821709.

In the 2000 paper, 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones were tested in vivo in the mouse passive avoidance test and shown to be a new class of nootropic agents with a profile very similar to piracetam and much higher potency, and compound 7 (DM 232) was active at 0.001 mg/kg subcutaneously. The abstract does not name the amnesic challenge.

Participants / model
Mice
Treatment
Subcutaneous
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

From the group that discovered the compound.

Read the original source
Mice: reversal of NBQX amnesia at 0.1 mg/kg; rat slices: increased synaptic transmission with unifiram

Animal study

Galeotti N et al. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(6):538-45. PMID 14600801.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner. No abstract shows unifiram binding to AMPA receptors. A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead (PMID 23733502), and no equivalent test of unifiram was found.

Participants / model
Mice; rat hippocampal slices
Treatment
Intraperitoneal in mice; tissue bath in slices
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect.

Read the original source
Inventor's 2016 account: not patented, sold online for healthy users, long-term toxicity unknown

Narrative review (preclinical literature)

Gualtieri F. J Enzyme Inhib Med Chem. 2016;31(2):187-94. PMID 25831025.

The 2016 review by Gualtieri says unifiram and sunifiram were not protected by a patent, and that about 12 years after their 2000 disclosure he found dozens of web sites offering them as drugs that improve cognition in healthy individuals, although only few preclinical studies were done and long-term toxicity was unknown. A 2022 review of smart drugs in healthy people names 'unifiram analogues' among the popular cognitive enhancers and says efficacy in healthy individuals is uncertain and reported improvement temporary (PMID 35366192; its harm statements are for the enhancer classes together, not for unifiram).

Participants / model
Healthy-user market; review literature
Treatment
Not applicable
Follow-up
Not applicable
Study design
Review articles
Funding
not stated in the source

Reviews, not studies of unifiram in people.

Read the original source
PubMed, 10 October 2026: 11 records, none gives unifiram to a person

PubMed search record

PubMed search run 10 October 2026: unifiram[tiab] OR DM-232[tiab] OR DM232[tiab] OR "DM 232"[tiab], with a follow-up query adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety.

The search returned 11 records and abstracts were read for all 11: 1 unrelated (the 2001 returned-drugs study), 6 chemistry or structure-activity papers, 1 pharmacology paper, the 2006 pharmacology review, and 2 market reviews. Adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety returned 5, none reporting unifiram given to a person. No unifiram pharmacokinetic, toxicology or safety study appears, and the newest unifiram pharmacology paper is from 2005 to 2006. No controlled human trial exists in the records reviewed.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source
PubChem: unifiram identity, the stereocenter, and how it differs from sunifiram

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 9861054, 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one (unifiram, DM-232).

Unifiram is PubChem CID 9861054, C13H15FN2O3S, 298.34 g/mol, CAS 272786-64-8 (listed among the synonyms), IUPAC name 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, with DM 232 among the synonyms. It is a bicyclic lactam with a sulfonamide. Sunifiram (DM-235) is a different molecule (CID 4223812, C14H18N2O2, 246.30 g/mol, an acylpiperazine), so the two share a research group and a test system, not a structure, and no source in the records reviewed shows they are interchangeable in dose or effect. Unifiram has a stereocenter; the (R)-(+) and (S)-(-) enantiomers differ in potency, and the PubChem name carries no stereodescriptor, so a vendor product may be a racemate. A PubMed query on the 'DM 232' spelling also matches an unrelated German study of returned drugs ('DM 232,920' is a price in marks), so literature searches need the name.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule; racemate or enantiomers
Follow-up
Not applicable
Study design
Chemical database record; original reports
Funding
not stated in the source

Identity record only. No public record ties any vendor material to the studied compound.

Read the original source

What is known about the safety of unifiram?

No human safety, pharmacokinetic or toxicology data exist for unifiram, and its discoverer says long-term toxicity was unknown while it was sold online. In mice DM 232 at 0.1 mg/kg did not affect rota-rod coordination or motility, an amnesic analog exists in the same series, and the identity of vendor material, racemate or not, is not established.

No record reports unifiram given to a person, so no human adverse event, tolerability, pharmacokinetic or interaction information exists. No pharmacokinetic, toxicology or safety study of unifiram appears among the 11 records reviewed.

A 2016 review by the discoverer says long-term toxicity was unknown while the molecules were sold online to healthy users. A 2022 review of smart drugs says harms are possible, mainly from the stimulant-type enhancers it covers, and its harm statements are not specific to unifiram.

In mice, DM 232 at 0.1 mg/kg i.p. did not affect rota-rod coordination or motility. That is an acute rodent finding and not a safety result in people.

Product identity is a separate concern. Unifiram has two enantiomers that differ in potency by 3-fold to 10-fold, a vendor product may be a racemate, the isopropylsulfonyl analog was amnesic, and sunifiram is a different molecule.

PubMed, 10 October 2026: 11 records, none gives unifiram to a person

PubMed search record

PubMed search run 10 October 2026: unifiram[tiab] OR DM-232[tiab] OR DM232[tiab] OR "DM 232"[tiab], with a follow-up query adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety.

The search returned 11 records and abstracts were read for all 11: 1 unrelated (the 2001 returned-drugs study), 6 chemistry or structure-activity papers, 1 pharmacology paper, the 2006 pharmacology review, and 2 market reviews. Adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety returned 5, none reporting unifiram given to a person. No unifiram pharmacokinetic, toxicology or safety study appears, and the newest unifiram pharmacology paper is from 2005 to 2006. No controlled human trial exists in the records reviewed.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source
Inventor's 2016 account: not patented, sold online for healthy users, long-term toxicity unknown

Narrative review (preclinical literature)

Gualtieri F. J Enzyme Inhib Med Chem. 2016;31(2):187-94. PMID 25831025.

The 2016 review by Gualtieri says unifiram and sunifiram were not protected by a patent, and that about 12 years after their 2000 disclosure he found dozens of web sites offering them as drugs that improve cognition in healthy individuals, although only few preclinical studies were done and long-term toxicity was unknown. A 2022 review of smart drugs in healthy people names 'unifiram analogues' among the popular cognitive enhancers and says efficacy in healthy individuals is uncertain and reported improvement temporary (PMID 35366192; its harm statements are for the enhancer classes together, not for unifiram).

Participants / model
Healthy-user market; review literature
Treatment
Not applicable
Follow-up
Not applicable
Study design
Review articles
Funding
not stated in the source

Reviews, not studies of unifiram in people.

Read the original source
Mice: reversal of NBQX amnesia at 0.1 mg/kg; rat slices: increased synaptic transmission with unifiram

Animal study

Galeotti N et al. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(6):538-45. PMID 14600801.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner. No abstract shows unifiram binding to AMPA receptors. A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead (PMID 23733502), and no equivalent test of unifiram was found.

Participants / model
Mice; rat hippocampal slices
Treatment
Intraperitoneal in mice; tissue bath in slices
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect.

Read the original source
R-(+) more potent than S-(-) by 3-fold to 10-fold; the isopropylsulfonyl analog was amnesic

Animal study

Martini E et al. Med Chem. 2005;1(5):473-80. PMID 16787332.

The (R)-(+) enantiomer of DM232 was more potent than the (S)-(-) enantiomer in the passive avoidance and social learning tests and in acetylcholine release from rat cerebral cortex, producing comparable effects at 3-fold to 10-fold lower doses (enantiomeric excess above 99.9%). The isopropylsulfonyl analog of unifiram was endowed with amnesic properties, and its two enantiomers had the same amnesic potency.

Participants / model
Mice; rat cerebral cortex
Treatment
Not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A vendor product that is racemic, or that contains a sulfonyl analog, would not match the single compound studied.

Read the original source

Why does unifiram sit in D tier?

Unifiram is the older, better-characterized of the pair in rodents, with an enantiomer-specific result and slice evidence, but all of it is from one academic group, with no human exposure, pharmacokinetics or toxicology, no independent replication of unifiram itself, and close analogs that are amnesic.

Unifiram is the older, better-characterized of the pair in rodents, with an enantiomer-specific result, evidence of increased hippocampal synaptic transmission in slices, and a potency far above piracetam in mouse amnesia tests, all from one academic group.

The data stop at mice, rats and tissue, with no human exposure, no pharmacokinetics, no toxicology and no independent replication of unifiram itself in the records reviewed; the 2013 independent work was on sunifiram. The discoverer says it is sold online for healthy users on few preclinical studies, and close analogs in the same series are amnesic.

R-(+) more potent than S-(-) by 3-fold to 10-fold; the isopropylsulfonyl analog was amnesic

Animal study

Martini E et al. Med Chem. 2005;1(5):473-80. PMID 16787332.

The (R)-(+) enantiomer of DM232 was more potent than the (S)-(-) enantiomer in the passive avoidance and social learning tests and in acetylcholine release from rat cerebral cortex, producing comparable effects at 3-fold to 10-fold lower doses (enantiomeric excess above 99.9%). The isopropylsulfonyl analog of unifiram was endowed with amnesic properties, and its two enantiomers had the same amnesic potency.

Participants / model
Mice; rat cerebral cortex
Treatment
Not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A vendor product that is racemic, or that contains a sulfonyl analog, would not match the single compound studied.

Read the original source
Mice: reversal of NBQX amnesia at 0.1 mg/kg; rat slices: increased synaptic transmission with unifiram

Animal study

Galeotti N et al. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(6):538-45. PMID 14600801.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner. No abstract shows unifiram binding to AMPA receptors. A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead (PMID 23733502), and no equivalent test of unifiram was found.

Participants / model
Mice; rat hippocampal slices
Treatment
Intraperitoneal in mice; tissue bath in slices
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect.

Read the original source
Inventor's 2016 account: not patented, sold online for healthy users, long-term toxicity unknown

Narrative review (preclinical literature)

Gualtieri F. J Enzyme Inhib Med Chem. 2016;31(2):187-94. PMID 25831025.

The 2016 review by Gualtieri says unifiram and sunifiram were not protected by a patent, and that about 12 years after their 2000 disclosure he found dozens of web sites offering them as drugs that improve cognition in healthy individuals, although only few preclinical studies were done and long-term toxicity was unknown. A 2022 review of smart drugs in healthy people names 'unifiram analogues' among the popular cognitive enhancers and says efficacy in healthy individuals is uncertain and reported improvement temporary (PMID 35366192; its harm statements are for the enhancer classes together, not for unifiram).

Participants / model
Healthy-user market; review literature
Treatment
Not applicable
Follow-up
Not applicable
Study design
Review articles
Funding
not stated in the source

Reviews, not studies of unifiram in people.

Read the original source
PubMed, 10 October 2026: 11 records, none gives unifiram to a person

PubMed search record

PubMed search run 10 October 2026: unifiram[tiab] OR DM-232[tiab] OR DM232[tiab] OR "DM 232"[tiab], with a follow-up query adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety.

The search returned 11 records and abstracts were read for all 11: 1 unrelated (the 2001 returned-drugs study), 6 chemistry or structure-activity papers, 1 pharmacology paper, the 2006 pharmacology review, and 2 market reviews. Adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety returned 5, none reporting unifiram given to a person. No unifiram pharmacokinetic, toxicology or safety study appears, and the newest unifiram pharmacology paper is from 2005 to 2006. No controlled human trial exists in the records reviewed.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source

Studies and sources

PubChem: unifiram identity, the stereocenter, and how it differs from sunifiram

Chemical identity record

PubChem, National Library of Medicine. Compound summary for CID 9861054, 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one (unifiram, DM-232).

Unifiram is PubChem CID 9861054, C13H15FN2O3S, 298.34 g/mol, CAS 272786-64-8 (listed among the synonyms), IUPAC name 2-(4-fluorophenyl)sulfonyl-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, with DM 232 among the synonyms. It is a bicyclic lactam with a sulfonamide. Sunifiram (DM-235) is a different molecule (CID 4223812, C14H18N2O2, 246.30 g/mol, an acylpiperazine), so the two share a research group and a test system, not a structure, and no source in the records reviewed shows they are interchangeable in dose or effect. Unifiram has a stereocenter; the (R)-(+) and (S)-(-) enantiomers differ in potency, and the PubChem name carries no stereodescriptor, so a vendor product may be a racemate. A PubMed query on the 'DM 232' spelling also matches an unrelated German study of returned drugs ('DM 232,920' is a price in marks), so literature searches need the name.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule; racemate or enantiomers
Follow-up
Not applicable
Study design
Chemical database record; original reports
Funding
not stated in the source

Identity record only. No public record ties any vendor material to the studied compound.

Read the original source
2000 discovery paper: DM 232 active at 0.001 mg/kg subcutaneously in mouse passive avoidance

Animal study

Manetti D et al. J Med Chem. 2000;43(10):1969-74. PMID 10821709.

In the 2000 paper, 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones were tested in vivo in the mouse passive avoidance test and shown to be a new class of nootropic agents with a profile very similar to piracetam and much higher potency, and compound 7 (DM 232) was active at 0.001 mg/kg subcutaneously. The abstract does not name the amnesic challenge.

Participants / model
Mice
Treatment
Subcutaneous
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

From the group that discovered the compound.

Read the original source
Discoverers' 2006 summary: four orders of magnitude over piracetam, no receptor binding, AMPA hypothesis

Narrative review (preclinical literature)

Romanelli MN et al. CNS Drug Rev. 2006;12(1):39-52. PMID 16834757.

A 2006 review by the discovering group says unifiram and sunifiram are four orders of magnitude more potent than piracetam, show no affinity in binding studies for the most important central receptors or channels, prevent amnesia induced by modulation of several neurotransmission systems, increase acetylcholine release from rat cerebral cortex, and, for unifiram, increase the amplitude of field excitatory postsynaptic potentials in rat hippocampal slices; slice experiments support a role for AMPA receptors.

Participants / model
Mice, rats, rat cortical and hippocampal tissue
Treatment
Not stated in the review abstract
Follow-up
not stated in the source
Study design
Review by the discovering group
Funding
not stated in the source

The potency comparison is against piracetam in mouse and rat amnesia tests, not against any approved cognitive drug in people.

Read the original source
Mice: reversal of NBQX amnesia at 0.1 mg/kg; rat slices: increased synaptic transmission with unifiram

Animal study

Galeotti N et al. Naunyn Schmiedebergs Arch Pharmacol. 2003;368(6):538-45. PMID 14600801.

In mice, DM 232 and DM 235 at 0.1 mg/kg i.p. reversed amnesia caused by the AMPA antagonist NBQX (30 mg/kg i.p.) in passive avoidance, without affecting rota-rod coordination or motility. In rat hippocampal slices both reversed kynurenic acid's block of NMDA-mediated [3H]noradrenaline release, an effect abolished by NBQX, and DM 232, but not DM 235 in that paper, increased excitatory synaptic transmission in a concentration-dependent manner. No abstract shows unifiram binding to AMPA receptors. A 2013 independent paper on sunifiram attributes its effect to the NMDA glycine site instead (PMID 23733502), and no equivalent test of unifiram was found.

Participants / model
Mice; rat hippocampal slices
Treatment
Intraperitoneal in mice; tissue bath in slices
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The AMPA evidence is stronger for unifiram than for sunifiram but is still indirect.

Read the original source
R-(+) more potent than S-(-) by 3-fold to 10-fold; the isopropylsulfonyl analog was amnesic

Animal study

Martini E et al. Med Chem. 2005;1(5):473-80. PMID 16787332.

The (R)-(+) enantiomer of DM232 was more potent than the (S)-(-) enantiomer in the passive avoidance and social learning tests and in acetylcholine release from rat cerebral cortex, producing comparable effects at 3-fold to 10-fold lower doses (enantiomeric excess above 99.9%). The isopropylsulfonyl analog of unifiram was endowed with amnesic properties, and its two enantiomers had the same amnesic potency.

Participants / model
Mice; rat cerebral cortex
Treatment
Not stated in the abstract
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A vendor product that is racemic, or that contains a sulfonyl analog, would not match the single compound studied.

Read the original source
Analog series: none matched the parents, two were amnesic, phenylpiperazines were less potent

Animal study

Scapecchi S et al. Bioorg Med Chem. 2004;12(1):71-85. PMID 14697772.

A structure-activity study reports that none of the compounds made reached the potency of unifiram and sunifiram and that two (numbered 13 and 14) had amnesic activity nearly equipotent to scopolamine. Later series made unifiram and sunifiram analogs with good antiamnestic activity and higher potency than piracetam, and reported that some cyclohexane derivatives induce amnesia (PMID 18954993). 2- and 3-phenylpiperazines related to DM235 and DM232 were less potent than the parents in reversing scopolamine-induced amnesia in mouse passive avoidance (PMID 25813160).

Participants / model
Mice
Treatment
Not stated in the abstracts
Follow-up
not stated in the source
Study design
Original chemistry and pharmacology studies
Funding
not stated in the source

The class is easy to push in either direction.

Read the original source
Inventor's 2016 account: not patented, sold online for healthy users, long-term toxicity unknown

Narrative review (preclinical literature)

Gualtieri F. J Enzyme Inhib Med Chem. 2016;31(2):187-94. PMID 25831025.

The 2016 review by Gualtieri says unifiram and sunifiram were not protected by a patent, and that about 12 years after their 2000 disclosure he found dozens of web sites offering them as drugs that improve cognition in healthy individuals, although only few preclinical studies were done and long-term toxicity was unknown. A 2022 review of smart drugs in healthy people names 'unifiram analogues' among the popular cognitive enhancers and says efficacy in healthy individuals is uncertain and reported improvement temporary (PMID 35366192; its harm statements are for the enhancer classes together, not for unifiram).

Participants / model
Healthy-user market; review literature
Treatment
Not applicable
Follow-up
Not applicable
Study design
Review articles
Funding
not stated in the source

Reviews, not studies of unifiram in people.

Read the original source
PubMed, 10 October 2026: 11 records, none gives unifiram to a person

PubMed search record

PubMed search run 10 October 2026: unifiram[tiab] OR DM-232[tiab] OR DM232[tiab] OR "DM 232"[tiab], with a follow-up query adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety.

The search returned 11 records and abstracts were read for all 11: 1 unrelated (the 2001 returned-drugs study), 6 chemistry or structure-activity papers, 1 pharmacology paper, the 2006 pharmacology review, and 2 market reviews. Adding human, humans, patients, volunteers, clinical, trial, pharmacokinetic*, toxicity or safety returned 5, none reporting unifiram given to a person. No unifiram pharmacokinetic, toxicology or safety study appears, and the newest unifiram pharmacology paper is from 2005 to 2006. No controlled human trial exists in the records reviewed.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated literature search
Funding
not stated in the source

An absence finding as of 10 October 2026, not proof that no unpublished or unindexed work exists.

Read the original source
Label and registry searches, 10 October 2026: no label, no match, no study

Regulatory record

U.S. Food and Drug Administration (DailyMed label search; openFDA Drugs@FDA query) and ClinicalTrials.gov. Searches for unifiram and for DM232 and DM-232, run 10 October 2026.

ClinicalTrials.gov queries for unifiram and for DM232 or DM-232 returned no studies, DailyMed returned no label for unifiram, and the openFDA Drugs@FDA query returned no match.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated label, application and registry search
Funding
not stated in the source

An absence finding as of 10 October 2026. It covers United States label, application and registry records only.

Read the original source

Why is Unifiram (DM-232) in D tier?

D fits the older and better-characterized of two related compounds in rodents, with an enantiomer-specific result, slice evidence and potency far above piracetam in mouse amnesia tests, all from one academic group. The data stop at mice, rats and tissue, with no human exposure, pharmacokinetics or toxicology and no independent replication of unifiram itself, and its discoverer says it is sold online to healthy users on few preclinical studies.