7,8-Dihydroxyflavone

updated

7,8-Dihydroxyflavone (7,8-DHF) is a research chemical sold as an oral TrkB agonist and BDNF mimetic for cognition and mood. Rodent studies report memory and antidepressant-like effects, but one found no benefit in Alzheimer model mice, and an independent laboratory found no TrkB activation in cells or mouse brain and poor oral exposure. No approval record, registered trial or published human study was found.

Flavone; claimed TrkB agonist, disputed

  • 7,8-Dihydroxyflavone is PubChem CID 1880, C15H10O4, 254.24 g/mol, CAS 38183-03-8.
  • No approval record, registered trial or published human study was found on 11 October 2026.
  • In aged rats, daily intraperitoneal 7,8-DHF for 2 weeks improved spatial memory in 22-month-old animals.
  • In Alzheimer model mice it did not reduce plaque deposition or improve learning and memory.
  • An independent 2021 study found no TrkB activation in cells or mouse brain and a brain peak of 6.35 ng/g after 50 mg/kg orally in mice.
  • Eutropoflavin (4'-DMA-7,8-DHF) is a different molecule, and data for one do not transfer to the other.

What is 7,8-dihydroxyflavone, and is it approved?

7,8-Dihydroxyflavone is a small-molecule flavone sold as a research chemical. No FDA application, label or registered study was found, and no record reviewed reports giving it to people.

7,8-Dihydroxyflavone is PubChem CID 1880, C15H10O4, 254.24 g/mol, CAS 38183-03-8. It is not the same molecule as 4'-dimethylamino-7,8-dihydroxyflavone (4'-DMA-7,8-DHF), which PubChem also lists as eutropoflavin: CID 44610701, C17H15NO4, 297.30 g/mol, with CAS numbers 1205548-04-4 and 1205548-00-0 on the record. That synthetic derivative was made to improve on 7,8-DHF, and data for one do not transfer to the other. A prodrug named R13 and two O-methylated metabolites are further distinct compounds.

On 11 October 2026 openFDA Drugs@FDA returned no application and DailyMed no label for 7,8-dihydroxyflavone, eutropoflavin or tropoflavin. ClinicalTrials.gov returned no study for any of the compound names; the abbreviation 7,8-DHF returned 2 unrelated studies, on dental anxiety in children and a post-operative run. A PubMed search for the compound names with clinical trial publication types returned 0 records, against 430 records for the names alone.

PubChem: 7,8-DHF and the distinct 4'-DMA derivative

Chemical identity record

National Library of Medicine. PubChem compound records CID 1880 (7,8-dihydroxyflavone) and CID 44610701 (4'-dimethylamino-7,8-dihydroxyflavone, eutropoflavin).

7,8-Dihydroxyflavone: C15H10O4, 254.24 g/mol, CAS 38183-03-8. 4'-DMA-7,8-DHF (eutropoflavin): C17H15NO4, 297.30 g/mol, CAS numbers 1205548-04-4 and 1205548-00-0 on the record, with a hydrobromide name also listed. The prodrug R13 and two O-methylated metabolites are further distinct compounds.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecules
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Which CAS number belongs to which form of the 4'-DMA derivative is not established. Data for 7,8-DHF and its derivative do not transfer to each other.

Read the original source
Searches, 11 October 2026: no approval, registered study or human trial

PubMed search record

PubMed search run on 11 October 2026: (7,8-dihydroxyflavone[tiab] OR 7,8-DHF[tiab] OR eutropoflavin[tiab] OR 4'-dimethylamino-7,8-dihydroxyflavone[tiab]) AND clinical trial publication types (clinical trial, randomized controlled trial, phase I, phase II). 0 records, against 430 for the names alone. With openFDA Drugs@FDA, DailyMed and ClinicalTrials.gov searches the same day.

openFDA returned no application and DailyMed no label for 7,8-dihydroxyflavone, eutropoflavin or tropoflavin. ClinicalTrials.gov returned no study for any compound name; the abbreviation 7,8-DHF returned 2 unrelated studies. The PubMed clinical trial search returned 0 records. No record reviewed reports giving 7,8-DHF or its derivatives to people, and no toxicology or safety study was found in the targeted searches.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Dated FDA, DailyMed, registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date.

Read the original source

What did the animal studies find?

In aged rats, 7,8-DHF improved spatial memory, and in mice under chronic stress, long-term treatment reversed depression-like behavior. In Alzheimer model mice it did not reduce plaques or improve learning and memory. Doses are missing from most abstracts, and no study has tested it in people.

In rats aged 22 and 30 months that were impaired on the Morris water maze, daily intraperitoneal 7,8-DHF for 2 weeks improved spatial memory in the 22-month-old rats, with more synapse formation and facilitated synaptic plasticity in the hippocampus. The 30-month-old rats needed more extended treatment for a significant improvement, and the effect was more pronounced in the younger impaired rats.

In mice exposed to chronic mild stress, long-term but not single-injection 7,8-DHF restored sucrose preference and novelty-suppressed feeding, raised TrkB phosphorylation and BDNF levels, and increased the synaptic proteins PSD95 and synaptophysin. The TrkB antagonist K252a blocked the effect. This is an animal model of depression-like behavior, not a depression outcome in people.

In a structure-activity study, chronic oral 7,8-DHF promoted neurogenesis in the dentate gyrus and showed antidepressant-like effects in animals; the abstract does not name the species or doses, and its senior author also led the original TrkB report. In APP23/PS45 Alzheimer model mice, 7,8-DHF had no significant effect on APP, BACE1 or amyloid beta, did not reduce plaque deposition and did not improve learning and memory.

Aged rats: memory improved at 22 months, slower at 30 months

Animal study

Zeng Y et al. J Neurochem. 2012;122(4):800-11. PMID 22694088.

Daily intraperitoneal 7,8-DHF for 2 weeks improved spatial memory in 22-month-old impaired rats, with more synapse formation and facilitated hippocampal synaptic plasticity. 30-month-old rats needed more extended treatment for a significant improvement, and the effect was more pronounced in the younger impaired rats.

Participants / model
Rats aged 22 and 30 months with cognitive impairment on the Morris water maze
Treatment
Intraperitoneal 7,8-DHF daily (dose not stated in the abstract)
Follow-up
2 weeks, or longer in 30-month-old rats
Study design
Original preclinical study
Funding
not stated in the source

Rat data, by injection; not an oral or human result.

Read the original source
Stressed mice: long-term treatment reversed depression-like behavior

Animal study

Zhang MW et al. Neurosci Lett. 2016;635:33-38. PMID 27773794.

Long-term but not single-injection 7,8-DHF restored sucrose preference and novelty-suppressed feeding, raised TrkB phosphorylation and BDNF levels, and increased PSD95 and synaptophysin. The TrkB antagonist K252a blocked the antidepressant-like effect.

Participants / model
Mice under chronic mild stress
Treatment
Injection of 7,8-DHF, single or long term (dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

An animal behavior model of depression, not a depression outcome in people.

Read the original source
Derivative study: oral 7,8-DHF and neurogenesis in animals

Animal study

Liu X et al. J Med Chem. 2010;53(23):8274-86. PMID 21073191.

Chronic oral 7,8-DHF promoted neurogenesis in the dentate gyrus and showed marked antidepressant effects, and the authors called it an orally bioavailable TrkB agonist. The same study made the 4'-dimethylamino derivative, a different molecule designed to improve on 7,8-DHF.

Participants / model
Animals; species not stated in the abstract
Treatment
Chronic oral administration (doses not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical structure-activity study
Funding
not stated in the source

The senior author is the same as in the original TrkB report. The oral bioavailability premise was later contested.

Read the original source
Alzheimer model mice: no effect on plaques or memory

Animal study

Zhou W et al. Curr Alzheimer Res. 2015;12(1):47-52. PMID 25523427.

7,8-DHF had no significant effect on APP, BACE1 or amyloid beta, did not reduce plaque deposition and did not alleviate learning and memory impairments; it also had little effect on APP processing in cell cultures.

Participants / model
APP23/PS45 Alzheimer model mice and cell cultures
Treatment
7,8-DHF treatment (route and dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A null result on cognition in an Alzheimer mouse model.

Read the original source

Is 7,8-DHF an oral BDNF mimetic that improves cognition and mood?

Not on current data. The cognition and mood results are animal findings only, independent work disputes both the TrkB agonist premise and good oral exposure, and nothing in the records reviewed tests the compound in people.

Sellers describe 7,8-DHF as an oral TrkB agonist that mimics BDNF and improves cognition and mood. The memory and mood results come from aged rats and stressed mice, and one Alzheimer mouse study was null. Pankiewicz and colleagues (2021) found no TrkB-dependent signaling in mouse brain and a brief, low exposure after an oral dose. No registered trial or published human study was found.

Aged rats: memory improved at 22 months, slower at 30 months

Animal study

Zeng Y et al. J Neurochem. 2012;122(4):800-11. PMID 22694088.

Daily intraperitoneal 7,8-DHF for 2 weeks improved spatial memory in 22-month-old impaired rats, with more synapse formation and facilitated hippocampal synaptic plasticity. 30-month-old rats needed more extended treatment for a significant improvement, and the effect was more pronounced in the younger impaired rats.

Participants / model
Rats aged 22 and 30 months with cognitive impairment on the Morris water maze
Treatment
Intraperitoneal 7,8-DHF daily (dose not stated in the abstract)
Follow-up
2 weeks, or longer in 30-month-old rats
Study design
Original preclinical study
Funding
not stated in the source

Rat data, by injection; not an oral or human result.

Read the original source
Stressed mice: long-term treatment reversed depression-like behavior

Animal study

Zhang MW et al. Neurosci Lett. 2016;635:33-38. PMID 27773794.

Long-term but not single-injection 7,8-DHF restored sucrose preference and novelty-suppressed feeding, raised TrkB phosphorylation and BDNF levels, and increased PSD95 and synaptophysin. The TrkB antagonist K252a blocked the antidepressant-like effect.

Participants / model
Mice under chronic mild stress
Treatment
Injection of 7,8-DHF, single or long term (dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

An animal behavior model of depression, not a depression outcome in people.

Read the original source
Alzheimer model mice: no effect on plaques or memory

Animal study

Zhou W et al. Curr Alzheimer Res. 2015;12(1):47-52. PMID 25523427.

7,8-DHF had no significant effect on APP, BACE1 or amyloid beta, did not reduce plaque deposition and did not alleviate learning and memory impairments; it also had little effect on APP processing in cell cultures.

Participants / model
APP23/PS45 Alzheimer model mice and cell cultures
Treatment
7,8-DHF treatment (route and dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A null result on cognition in an Alzheimer mouse model.

Read the original source
Pankiewicz 2021: Kd 1.3 micromolar, no TrkB activation, poor exposure

Animal study

Pankiewicz P et al. Pharmaceuticals (Basel). 2021;14(8). PMID 34451801.

7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice given 1 mg/kg intravenously or 50 mg/kg orally, pharmacokinetics were poor and there was no TrkB-dependent signaling in the brain. A binding screen against 133 targets showed a lack of selectivity. After the oral dose, plasma peaked at 77.43 ng/mL at the first sample (10 minutes) and fell below detection by 1 hour, brain peaked at 6.35 ng/g, and the intravenous dose was not detectable in plasma or brain.

Participants / model
Cell lines (SN56 T48, SH-SY5Y); mice
Treatment
In vitro exposure; intravenous 1 mg/kg and oral 50 mg/kg in mice
Follow-up
Plasma and brain sampled from 10 minutes after dosing
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The authors concluded 7,8-DHF is not a relevant tool for studying TrkB activation in vivo and that it and other published reference compounds do not activate TrkB. Exposure figures are from the full text.

Read the original source
Searches, 11 October 2026: no approval, registered study or human trial

PubMed search record

PubMed search run on 11 October 2026: (7,8-dihydroxyflavone[tiab] OR 7,8-DHF[tiab] OR eutropoflavin[tiab] OR 4'-dimethylamino-7,8-dihydroxyflavone[tiab]) AND clinical trial publication types (clinical trial, randomized controlled trial, phase I, phase II). 0 records, against 430 for the names alone. With openFDA Drugs@FDA, DailyMed and ClinicalTrials.gov searches the same day.

openFDA returned no application and DailyMed no label for 7,8-dihydroxyflavone, eutropoflavin or tropoflavin. ClinicalTrials.gov returned no study for any compound name; the abbreviation 7,8-DHF returned 2 unrelated studies. The PubMed clinical trial search returned 0 records. No record reviewed reports giving 7,8-DHF or its derivatives to people, and no toxicology or safety study was found in the targeted searches.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Dated FDA, DailyMed, registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date.

Read the original source

How was 7,8-DHF said to work?

The original report described 7,8-DHF as a high-affinity TrkB agonist that triggered receptor signaling and protected neurons in a TrkB-dependent way. A later study showed it directly inhibits a different enzyme, pyridoxal phosphatase, which offers another possible mechanism.

The first report identified 7,8-DHF as a high-affinity TrkB agonist that provoked receptor dimerization, autophosphorylation and downstream signaling. It protected wild-type but not TrkB-deficient neurons from apoptosis. In mice it activated TrkB in the brain, inhibited kainic acid toxicity, reduced stroke infarct volume in a TrkB-dependent manner and was neuroprotective in a Parkinson disease model. The abstract does not state doses or routes.

Screening, crystallography and biolayer interferometry later identified 7,8-DHF as a direct, reversible inhibitor of pyridoxal phosphatase (PDXP), with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons it raised pyridoxal 5'-phosphate, the active form of vitamin B6, in a PDXP-dependent manner. This shows an alternative mechanism, not that it explains the animal behavior results.

Original TrkB report: neurons and mouse injury models

Animal study

Jang SW et al. Proc Natl Acad Sci U S A. 2010;107(6):2687-92. PMID 20133810.

7,8-DHF was identified as a high-affinity TrkB agonist that provoked receptor dimerization, autophosphorylation and downstream signaling, and protected wild-type but not TrkB-deficient neurons from apoptosis. In mice it activated TrkB in the brain, inhibited kainic acid toxicity, reduced infarct volume in stroke in a TrkB-dependent manner, and was neuroprotective in a Parkinson disease model.

Participants / model
Cultured neurons; mice in kainic acid, stroke and Parkinson disease models
Treatment
In vitro exposure; administration to mice (route and dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The source of the TrkB agonist claim; independent laboratories later disputed it.

Read the original source
PDXP study: 7,8-DHF inhibits pyridoxal phosphatase

Cell study

Brenner M et al. Elife. 2024;13. PMID 38856179.

Screening, crystallography and biolayer interferometry identified 7,8-DHF as a direct, reversible PDXP inhibitor with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons it raised pyridoxal 5'-phosphate in a PDXP-dependent manner.

Participants / model
Purified enzyme; mouse hippocampal neurons
Treatment
In vitro exposure
Follow-up
Not applicable
Study design
Original study
Funding
not stated in the source

The authors say the finding offers mechanistic insight into the controversy over how 7,8-DHF acts in the brain. It shows an alternative mechanism, not that it explains the animal behavior results.

Read the original source

Do independent laboratories confirm that it activates TrkB?

No. Pankiewicz and colleagues (2021) found that 7,8-DHF bound TrkB with a Kd of 1.3 micromolar but did not activate it in two cell lines or produce TrkB-dependent signaling in mouse brain, and concluded it is not a relevant tool for studying TrkB activation in living animals.

In a study independent of the agonist's discoverers, 7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice it gave no TrkB-dependent signaling in the brain, and a binding screen against 133 targets showed a lack of selectivity. The authors concluded that 7,8-DHF and other published reference compounds do not activate TrkB.

A 2017 study using quantitative assays of TrkB activation, signaling and gene expression could not reproduce activity with reported small-molecule TrkB agonists, while BDNF and other neurotrophic factors gave robust dose-dependent activation. Its abstract does not name the compounds tested; the 2021 paper describes it as contradicting the postulated mechanism.

Pankiewicz 2021: Kd 1.3 micromolar, no TrkB activation, poor exposure

Animal study

Pankiewicz P et al. Pharmaceuticals (Basel). 2021;14(8). PMID 34451801.

7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice given 1 mg/kg intravenously or 50 mg/kg orally, pharmacokinetics were poor and there was no TrkB-dependent signaling in the brain. A binding screen against 133 targets showed a lack of selectivity. After the oral dose, plasma peaked at 77.43 ng/mL at the first sample (10 minutes) and fell below detection by 1 hour, brain peaked at 6.35 ng/g, and the intravenous dose was not detectable in plasma or brain.

Participants / model
Cell lines (SN56 T48, SH-SY5Y); mice
Treatment
In vitro exposure; intravenous 1 mg/kg and oral 50 mg/kg in mice
Follow-up
Plasma and brain sampled from 10 minutes after dosing
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The authors concluded 7,8-DHF is not a relevant tool for studying TrkB activation in vivo and that it and other published reference compounds do not activate TrkB. Exposure figures are from the full text.

Read the original source
Boltaev 2017: reported small-molecule agonists did not activate TrkB

Cell study

Boltaev U et al. Sci Signal. 2017;10(493). PMID 28831019.

BDNF and other neurotrophic factors produced robust dose-dependent TrkB activation, but the authors could not reproduce these activities with the reported small-molecule TrkB agonists and said results with these compounds must be carefully interpreted.

Participants / model
Cell-based assays
Treatment
In vitro exposure
Follow-up
Not applicable
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The abstract does not name the compounds tested. The 2021 Pankiewicz paper describes this study as contradicting the postulated mechanism; it is context, not a direct test of 7,8-DHF named in the abstract.

Read the original source

How much reaches the brain after an oral dose in mice?

In the one mouse study that measured it, exposure was poor by the authors' account. After 50 mg/kg by mouth, plasma peaked at the first 10-minute sample and fell below detection by 1 hour, and brain levels peaked at 6.35 ng/g. No human exposure data exist.

In the 2021 study, mice given 50 mg/kg orally reached a plasma peak of 77.43 ng/mL at the first sample, 10 minutes after dosing, and plasma fell below detection by 1 hour. Brain levels peaked at 6.35 ng/g. After 1 mg/kg intravenously, 7,8-DHF was not detectable in plasma or brain. The authors described its pharmacokinetics as poor.

Pankiewicz 2021: Kd 1.3 micromolar, no TrkB activation, poor exposure

Animal study

Pankiewicz P et al. Pharmaceuticals (Basel). 2021;14(8). PMID 34451801.

7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice given 1 mg/kg intravenously or 50 mg/kg orally, pharmacokinetics were poor and there was no TrkB-dependent signaling in the brain. A binding screen against 133 targets showed a lack of selectivity. After the oral dose, plasma peaked at 77.43 ng/mL at the first sample (10 minutes) and fell below detection by 1 hour, brain peaked at 6.35 ng/g, and the intravenous dose was not detectable in plasma or brain.

Participants / model
Cell lines (SN56 T48, SH-SY5Y); mice
Treatment
In vitro exposure; intravenous 1 mg/kg and oral 50 mg/kg in mice
Follow-up
Plasma and brain sampled from 10 minutes after dosing
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The authors concluded 7,8-DHF is not a relevant tool for studying TrkB activation in vivo and that it and other published reference compounds do not activate TrkB. Exposure figures are from the full text.

Read the original source

What is known about the safety of 7,8-DHF?

Nothing in people. No record reviewed reports giving 7,8-DHF to humans, and no toxicology or safety study was found, so its human safety is unknown. A binding screen showed a lack of selectivity, and related molecules sold under similar names are different compounds.

Targeted searches found no toxicology or safety study of 7,8-DHF and no study that gave it to people, so this page makes no claim that it is safe or unsafe. A binding screen against 133 targets showed a lack of selectivity, and the compound also inhibits pyridoxal phosphatase.

Eutropoflavin (4'-DMA-7,8-DHF), the prodrug R13 and O-methylated metabolites are distinct molecules, so a product's identity cannot be assumed from a similar name.

Searches, 11 October 2026: no approval, registered study or human trial

PubMed search record

PubMed search run on 11 October 2026: (7,8-dihydroxyflavone[tiab] OR 7,8-DHF[tiab] OR eutropoflavin[tiab] OR 4'-dimethylamino-7,8-dihydroxyflavone[tiab]) AND clinical trial publication types (clinical trial, randomized controlled trial, phase I, phase II). 0 records, against 430 for the names alone. With openFDA Drugs@FDA, DailyMed and ClinicalTrials.gov searches the same day.

openFDA returned no application and DailyMed no label for 7,8-dihydroxyflavone, eutropoflavin or tropoflavin. ClinicalTrials.gov returned no study for any compound name; the abbreviation 7,8-DHF returned 2 unrelated studies. The PubMed clinical trial search returned 0 records. No record reviewed reports giving 7,8-DHF or its derivatives to people, and no toxicology or safety study was found in the targeted searches.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Dated FDA, DailyMed, registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date.

Read the original source
Pankiewicz 2021: Kd 1.3 micromolar, no TrkB activation, poor exposure

Animal study

Pankiewicz P et al. Pharmaceuticals (Basel). 2021;14(8). PMID 34451801.

7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice given 1 mg/kg intravenously or 50 mg/kg orally, pharmacokinetics were poor and there was no TrkB-dependent signaling in the brain. A binding screen against 133 targets showed a lack of selectivity. After the oral dose, plasma peaked at 77.43 ng/mL at the first sample (10 minutes) and fell below detection by 1 hour, brain peaked at 6.35 ng/g, and the intravenous dose was not detectable in plasma or brain.

Participants / model
Cell lines (SN56 T48, SH-SY5Y); mice
Treatment
In vitro exposure; intravenous 1 mg/kg and oral 50 mg/kg in mice
Follow-up
Plasma and brain sampled from 10 minutes after dosing
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The authors concluded 7,8-DHF is not a relevant tool for studying TrkB activation in vivo and that it and other published reference compounds do not activate TrkB. Exposure figures are from the full text.

Read the original source
PDXP study: 7,8-DHF inhibits pyridoxal phosphatase

Cell study

Brenner M et al. Elife. 2024;13. PMID 38856179.

Screening, crystallography and biolayer interferometry identified 7,8-DHF as a direct, reversible PDXP inhibitor with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons it raised pyridoxal 5'-phosphate in a PDXP-dependent manner.

Participants / model
Purified enzyme; mouse hippocampal neurons
Treatment
In vitro exposure
Follow-up
Not applicable
Study design
Original study
Funding
not stated in the source

The authors say the finding offers mechanistic insight into the controversy over how 7,8-DHF acts in the brain. It shows an alternative mechanism, not that it explains the animal behavior results.

Read the original source
PubChem: 7,8-DHF and the distinct 4'-DMA derivative

Chemical identity record

National Library of Medicine. PubChem compound records CID 1880 (7,8-dihydroxyflavone) and CID 44610701 (4'-dimethylamino-7,8-dihydroxyflavone, eutropoflavin).

7,8-Dihydroxyflavone: C15H10O4, 254.24 g/mol, CAS 38183-03-8. 4'-DMA-7,8-DHF (eutropoflavin): C17H15NO4, 297.30 g/mol, CAS numbers 1205548-04-4 and 1205548-00-0 on the record, with a hydrobromide name also listed. The prodrug R13 and two O-methylated metabolites are further distinct compounds.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecules
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Which CAS number belongs to which form of the 4'-DMA derivative is not established. Data for 7,8-DHF and its derivative do not transfer to each other.

Read the original source

Why does 7,8-DHF sit in D tier?

D fits a research chemical with a large animal literature but a disputed mechanism, poor oral exposure in mice, a null Alzheimer mouse study and no human study, approval record or registered trial. A C is arguable because the animal results are broad and come from several laboratories.

PubMed holds 430 records for the compound names, with positive memory and mood results in aged rats and stressed mice. Against them, independent laboratories dispute TrkB activation, a direct exposure study found a brain peak of 6.35 ng/g after 50 mg/kg orally in mice, an alternative target has been shown, and no person has been given the compound in any study found.

Searches, 11 October 2026: no approval, registered study or human trial

PubMed search record

PubMed search run on 11 October 2026: (7,8-dihydroxyflavone[tiab] OR 7,8-DHF[tiab] OR eutropoflavin[tiab] OR 4'-dimethylamino-7,8-dihydroxyflavone[tiab]) AND clinical trial publication types (clinical trial, randomized controlled trial, phase I, phase II). 0 records, against 430 for the names alone. With openFDA Drugs@FDA, DailyMed and ClinicalTrials.gov searches the same day.

openFDA returned no application and DailyMed no label for 7,8-dihydroxyflavone, eutropoflavin or tropoflavin. ClinicalTrials.gov returned no study for any compound name; the abbreviation 7,8-DHF returned 2 unrelated studies. The PubMed clinical trial search returned 0 records. No record reviewed reports giving 7,8-DHF or its derivatives to people, and no toxicology or safety study was found in the targeted searches.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Dated FDA, DailyMed, registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date.

Read the original source
Aged rats: memory improved at 22 months, slower at 30 months

Animal study

Zeng Y et al. J Neurochem. 2012;122(4):800-11. PMID 22694088.

Daily intraperitoneal 7,8-DHF for 2 weeks improved spatial memory in 22-month-old impaired rats, with more synapse formation and facilitated hippocampal synaptic plasticity. 30-month-old rats needed more extended treatment for a significant improvement, and the effect was more pronounced in the younger impaired rats.

Participants / model
Rats aged 22 and 30 months with cognitive impairment on the Morris water maze
Treatment
Intraperitoneal 7,8-DHF daily (dose not stated in the abstract)
Follow-up
2 weeks, or longer in 30-month-old rats
Study design
Original preclinical study
Funding
not stated in the source

Rat data, by injection; not an oral or human result.

Read the original source
Stressed mice: long-term treatment reversed depression-like behavior

Animal study

Zhang MW et al. Neurosci Lett. 2016;635:33-38. PMID 27773794.

Long-term but not single-injection 7,8-DHF restored sucrose preference and novelty-suppressed feeding, raised TrkB phosphorylation and BDNF levels, and increased PSD95 and synaptophysin. The TrkB antagonist K252a blocked the antidepressant-like effect.

Participants / model
Mice under chronic mild stress
Treatment
Injection of 7,8-DHF, single or long term (dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

An animal behavior model of depression, not a depression outcome in people.

Read the original source
Alzheimer model mice: no effect on plaques or memory

Animal study

Zhou W et al. Curr Alzheimer Res. 2015;12(1):47-52. PMID 25523427.

7,8-DHF had no significant effect on APP, BACE1 or amyloid beta, did not reduce plaque deposition and did not alleviate learning and memory impairments; it also had little effect on APP processing in cell cultures.

Participants / model
APP23/PS45 Alzheimer model mice and cell cultures
Treatment
7,8-DHF treatment (route and dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A null result on cognition in an Alzheimer mouse model.

Read the original source
Pankiewicz 2021: Kd 1.3 micromolar, no TrkB activation, poor exposure

Animal study

Pankiewicz P et al. Pharmaceuticals (Basel). 2021;14(8). PMID 34451801.

7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice given 1 mg/kg intravenously or 50 mg/kg orally, pharmacokinetics were poor and there was no TrkB-dependent signaling in the brain. A binding screen against 133 targets showed a lack of selectivity. After the oral dose, plasma peaked at 77.43 ng/mL at the first sample (10 minutes) and fell below detection by 1 hour, brain peaked at 6.35 ng/g, and the intravenous dose was not detectable in plasma or brain.

Participants / model
Cell lines (SN56 T48, SH-SY5Y); mice
Treatment
In vitro exposure; intravenous 1 mg/kg and oral 50 mg/kg in mice
Follow-up
Plasma and brain sampled from 10 minutes after dosing
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The authors concluded 7,8-DHF is not a relevant tool for studying TrkB activation in vivo and that it and other published reference compounds do not activate TrkB. Exposure figures are from the full text.

Read the original source
PDXP study: 7,8-DHF inhibits pyridoxal phosphatase

Cell study

Brenner M et al. Elife. 2024;13. PMID 38856179.

Screening, crystallography and biolayer interferometry identified 7,8-DHF as a direct, reversible PDXP inhibitor with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons it raised pyridoxal 5'-phosphate in a PDXP-dependent manner.

Participants / model
Purified enzyme; mouse hippocampal neurons
Treatment
In vitro exposure
Follow-up
Not applicable
Study design
Original study
Funding
not stated in the source

The authors say the finding offers mechanistic insight into the controversy over how 7,8-DHF acts in the brain. It shows an alternative mechanism, not that it explains the animal behavior results.

Read the original source

Studies and sources

PubChem: 7,8-DHF and the distinct 4'-DMA derivative

Chemical identity record

National Library of Medicine. PubChem compound records CID 1880 (7,8-dihydroxyflavone) and CID 44610701 (4'-dimethylamino-7,8-dihydroxyflavone, eutropoflavin).

7,8-Dihydroxyflavone: C15H10O4, 254.24 g/mol, CAS 38183-03-8. 4'-DMA-7,8-DHF (eutropoflavin): C17H15NO4, 297.30 g/mol, CAS numbers 1205548-04-4 and 1205548-00-0 on the record, with a hydrobromide name also listed. The prodrug R13 and two O-methylated metabolites are further distinct compounds.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecules
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Which CAS number belongs to which form of the 4'-DMA derivative is not established. Data for 7,8-DHF and its derivative do not transfer to each other.

Read the original source
Searches, 11 October 2026: no approval, registered study or human trial

PubMed search record

PubMed search run on 11 October 2026: (7,8-dihydroxyflavone[tiab] OR 7,8-DHF[tiab] OR eutropoflavin[tiab] OR 4'-dimethylamino-7,8-dihydroxyflavone[tiab]) AND clinical trial publication types (clinical trial, randomized controlled trial, phase I, phase II). 0 records, against 430 for the names alone. With openFDA Drugs@FDA, DailyMed and ClinicalTrials.gov searches the same day.

openFDA returned no application and DailyMed no label for 7,8-dihydroxyflavone, eutropoflavin or tropoflavin. ClinicalTrials.gov returned no study for any compound name; the abbreviation 7,8-DHF returned 2 unrelated studies. The PubMed clinical trial search returned 0 records. No record reviewed reports giving 7,8-DHF or its derivatives to people, and no toxicology or safety study was found in the targeted searches.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Searches run on 11 October 2026
Study design
Dated FDA, DailyMed, registry and literature searches
Funding
not stated in the source

A search result shows what the databases returned on that date.

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Original TrkB report: neurons and mouse injury models

Animal study

Jang SW et al. Proc Natl Acad Sci U S A. 2010;107(6):2687-92. PMID 20133810.

7,8-DHF was identified as a high-affinity TrkB agonist that provoked receptor dimerization, autophosphorylation and downstream signaling, and protected wild-type but not TrkB-deficient neurons from apoptosis. In mice it activated TrkB in the brain, inhibited kainic acid toxicity, reduced infarct volume in stroke in a TrkB-dependent manner, and was neuroprotective in a Parkinson disease model.

Participants / model
Cultured neurons; mice in kainic acid, stroke and Parkinson disease models
Treatment
In vitro exposure; administration to mice (route and dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

The source of the TrkB agonist claim; independent laboratories later disputed it.

Read the original source
Derivative study: oral 7,8-DHF and neurogenesis in animals

Animal study

Liu X et al. J Med Chem. 2010;53(23):8274-86. PMID 21073191.

Chronic oral 7,8-DHF promoted neurogenesis in the dentate gyrus and showed marked antidepressant effects, and the authors called it an orally bioavailable TrkB agonist. The same study made the 4'-dimethylamino derivative, a different molecule designed to improve on 7,8-DHF.

Participants / model
Animals; species not stated in the abstract
Treatment
Chronic oral administration (doses not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical structure-activity study
Funding
not stated in the source

The senior author is the same as in the original TrkB report. The oral bioavailability premise was later contested.

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Aged rats: memory improved at 22 months, slower at 30 months

Animal study

Zeng Y et al. J Neurochem. 2012;122(4):800-11. PMID 22694088.

Daily intraperitoneal 7,8-DHF for 2 weeks improved spatial memory in 22-month-old impaired rats, with more synapse formation and facilitated hippocampal synaptic plasticity. 30-month-old rats needed more extended treatment for a significant improvement, and the effect was more pronounced in the younger impaired rats.

Participants / model
Rats aged 22 and 30 months with cognitive impairment on the Morris water maze
Treatment
Intraperitoneal 7,8-DHF daily (dose not stated in the abstract)
Follow-up
2 weeks, or longer in 30-month-old rats
Study design
Original preclinical study
Funding
not stated in the source

Rat data, by injection; not an oral or human result.

Read the original source
Stressed mice: long-term treatment reversed depression-like behavior

Animal study

Zhang MW et al. Neurosci Lett. 2016;635:33-38. PMID 27773794.

Long-term but not single-injection 7,8-DHF restored sucrose preference and novelty-suppressed feeding, raised TrkB phosphorylation and BDNF levels, and increased PSD95 and synaptophysin. The TrkB antagonist K252a blocked the antidepressant-like effect.

Participants / model
Mice under chronic mild stress
Treatment
Injection of 7,8-DHF, single or long term (dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

An animal behavior model of depression, not a depression outcome in people.

Read the original source
Alzheimer model mice: no effect on plaques or memory

Animal study

Zhou W et al. Curr Alzheimer Res. 2015;12(1):47-52. PMID 25523427.

7,8-DHF had no significant effect on APP, BACE1 or amyloid beta, did not reduce plaque deposition and did not alleviate learning and memory impairments; it also had little effect on APP processing in cell cultures.

Participants / model
APP23/PS45 Alzheimer model mice and cell cultures
Treatment
7,8-DHF treatment (route and dose not stated in the abstract)
Follow-up
not stated in the source
Study design
Original preclinical study
Funding
not stated in the source

A null result on cognition in an Alzheimer mouse model.

Read the original source
Pankiewicz 2021: Kd 1.3 micromolar, no TrkB activation, poor exposure

Animal study

Pankiewicz P et al. Pharmaceuticals (Basel). 2021;14(8). PMID 34451801.

7,8-DHF bound TrkB with a Kd of 1.3 micromolar, but no other activity against TrkB was seen in SN56 T48 or differentiated SH-SY5Y cells. In mice given 1 mg/kg intravenously or 50 mg/kg orally, pharmacokinetics were poor and there was no TrkB-dependent signaling in the brain. A binding screen against 133 targets showed a lack of selectivity. After the oral dose, plasma peaked at 77.43 ng/mL at the first sample (10 minutes) and fell below detection by 1 hour, brain peaked at 6.35 ng/g, and the intravenous dose was not detectable in plasma or brain.

Participants / model
Cell lines (SN56 T48, SH-SY5Y); mice
Treatment
In vitro exposure; intravenous 1 mg/kg and oral 50 mg/kg in mice
Follow-up
Plasma and brain sampled from 10 minutes after dosing
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The authors concluded 7,8-DHF is not a relevant tool for studying TrkB activation in vivo and that it and other published reference compounds do not activate TrkB. Exposure figures are from the full text.

Read the original source
Boltaev 2017: reported small-molecule agonists did not activate TrkB

Cell study

Boltaev U et al. Sci Signal. 2017;10(493). PMID 28831019.

BDNF and other neurotrophic factors produced robust dose-dependent TrkB activation, but the authors could not reproduce these activities with the reported small-molecule TrkB agonists and said results with these compounds must be carefully interpreted.

Participants / model
Cell-based assays
Treatment
In vitro exposure
Follow-up
Not applicable
Study design
Original study independent of the agonist's discoverers
Funding
not stated in the source

The abstract does not name the compounds tested. The 2021 Pankiewicz paper describes this study as contradicting the postulated mechanism; it is context, not a direct test of 7,8-DHF named in the abstract.

Read the original source
PDXP study: 7,8-DHF inhibits pyridoxal phosphatase

Cell study

Brenner M et al. Elife. 2024;13. PMID 38856179.

Screening, crystallography and biolayer interferometry identified 7,8-DHF as a direct, reversible PDXP inhibitor with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons it raised pyridoxal 5'-phosphate in a PDXP-dependent manner.

Participants / model
Purified enzyme; mouse hippocampal neurons
Treatment
In vitro exposure
Follow-up
Not applicable
Study design
Original study
Funding
not stated in the source

The authors say the finding offers mechanistic insight into the controversy over how 7,8-DHF acts in the brain. It shows an alternative mechanism, not that it explains the animal behavior results.

Read the original source

Why is 7,8-Dihydroxyflavone in D tier?

D fits a research chemical whose cognition and mood results come only from animals, while the TrkB mechanism behind the claim is disputed by independent laboratories, oral exposure in mice was poor, and no study found has given it to people. A C is arguable because the animal results are broad and come from several laboratories.