Human dopamine transporter / DAT / SLC6A3

evidence_access

Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.

experimental_model

Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

armodafinil had radioligand-displacement Ki 0.78 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.

primary_references

R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. | 2012 | DOI 10.1016/j.biopsych.2012.03.022 | PMID 22537794 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/ | https://pubmed.ncbi.nlm.nih.gov/22537794/

source_locator

Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 40–46

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds. · Recorded from source · Recorded from source

| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM | |---|---:|---:| | Racemic modafinil | 13 | 2.3 | | R-modafinil | 4.0 | 0.78 | | S-modafinil | 8.7 | 2.5 | These are reported point estimates, not interchangeable constants. Uptake inhibition and equilibrium binding differ. The racemate's result should not be replaced by a calculated average of its enantiomers. [2012 study, Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/)

evidence_access

Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.

experimental_model

Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

armodafinil had dopamine uptake IC50 4.0 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.

primary_references

R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. | 2012 | DOI 10.1016/j.biopsych.2012.03.022 | PMID 22537794 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/ | https://pubmed.ncbi.nlm.nih.gov/22537794/

source_locator

Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 40–46

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds. · Recorded from source · Recorded from source

| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM | |---|---:|---:| | Racemic modafinil | 13 | 2.3 | | R-modafinil | 4.0 | 0.78 | | S-modafinil | 8.7 | 2.5 | These are reported point estimates, not interchangeable constants. Uptake inhibition and equilibrium binding differ. The racemate's result should not be replaced by a calculated average of its enantiomers. [2012 study, Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/)

evidence_access

Full XML obtained; relevant results/methods inspected. Not exhaustive reanalysis of figures or data.

experimental_model

Transporter mutation, ligand binding and modeling study.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

Mutational/modeling experiments support modafinil compatibility with DAT closed toward the extracellular side, not a permanently locked conformation in patients.

primary_references

The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. | 2011 | DOI 10.1371/journal.pone.0025790 | PMID 22043293 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3197159/ | https://pubmed.ncbi.nlm.nih.gov/22043293/

source_locator

Reviewed reference lines 54-54; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 54–54

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Transporter mutation, ligand binding and modeling study. · Recorded from source · Recorded from source

Mutational and modeling experiments distinguish modafinil from cocaine-like DAT inhibitors. The evidence supports greater compatibility with a transporter closed toward the extracellular side; it does not demonstrate a permanent, uniquely fixed conformation in patients. [2011 conformation study](https://pubmed.ncbi.nlm.nih.gov/22043293/)

evidence_access

Primary indexed abstract checked; full methods and figures not comprehensively reviewed.

experimental_contrast

{"intervention": "Oral modafinil 200 or 400 mg", "comparator": "Baseline/placebo comparison", "endpoint": "In ten healthy men, 200 or 400 mg oral modafinil reduced DAT-radiotracer binding by about 54% in caudate, 47% in putamen and 39% in nucleus accumbens.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human PET, ten healthy men; transporter occupancy is not percent dopamine increase.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

In ten healthy men, 200 or 400 mg oral modafinil reduced DAT-radiotracer binding by about 54% in caudate, 47% in putamen and 39% in nucleus accumbens.

primary_references

Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. | 2009 | DOI 10.1001/jama.2009.351 | PMID 19293415 | https://pubmed.ncbi.nlm.nih.gov/19293415/

source_locator

Reviewed reference lines 36-36; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 36–36

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human PET, ten healthy men; transporter occupancy is not percent dopamine increase. · Recorded from source · Recorded from source

In a PET study of **10 healthy men**, oral 200 or 400 mg modafinil reduced transporter-radiotracer binding by approximately **54% in caudate, 47% in putamen and 39% in nucleus accumbens**. Separate raclopride measurements supported increased extracellular dopamine. DAT occupancy is not a percentage increase in dopamine; raclopride displacement is an indirect imaging indicator rather than direct chemical sampling. [Volkow et al., 2009](https://pubmed.ncbi.nlm.nih.gov/19293415/)

evidence_access

Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.

experimental_model

Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

modafinil had radioligand-displacement Ki 2.3 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.

primary_references

R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. | 2012 | DOI 10.1016/j.biopsych.2012.03.022 | PMID 22537794 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/ | https://pubmed.ncbi.nlm.nih.gov/22537794/

source_locator

Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 40–46

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds. · Recorded from source · Recorded from source

| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM | |---|---:|---:| | Racemic modafinil | 13 | 2.3 | | R-modafinil | 4.0 | 0.78 | | S-modafinil | 8.7 | 2.5 | These are reported point estimates, not interchangeable constants. Uptake inhibition and equilibrium binding differ. The racemate's result should not be replaced by a calculated average of its enantiomers. [2012 study, Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/)

evidence_access

Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.

experimental_model

Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

modafinil had dopamine uptake IC50 13 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.

primary_references

R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. | 2012 | DOI 10.1016/j.biopsych.2012.03.022 | PMID 22537794 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/ | https://pubmed.ncbi.nlm.nih.gov/22537794/

source_locator

Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 40–46

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds. · Recorded from source · Recorded from source

| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM | |---|---:|---:| | Racemic modafinil | 13 | 2.3 | | R-modafinil | 4.0 | 0.78 | | S-modafinil | 8.7 | 2.5 | These are reported point estimates, not interchangeable constants. Uptake inhibition and equilibrium binding differ. The racemate's result should not be replaced by a calculated average of its enantiomers. [2012 study, Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/)

evidence_access

Primary abstract and publisher experimental procedures, results and discussion inspected; no supplementary-data reanalysis.

experimental_model

DAT-current recovery after inhibitor removal; transporter construct details remain in primary paper, not asserted as human clinical kinetics.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

s-mk-26 was among the more slowly dissociating modafinil analogues in the 2026 DAT-current-recovery experiments; plasma persistence and target residence are separate.

primary_references

Optimizing cognitive enhancement through dopamine transporter modulation. | 2026 | DOI 10.1016/j.neuropharm.2026.110969 | PMID 41980668 | https://doi.org/10.1016/j.neuropharm.2026.110969

source_locator

Reviewed reference lines 67-67; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 67–67

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · DAT-current recovery after inhibitor removal; transporter construct details remain in primary paper, not asserted as human clinical kinetics. · Recorded from source · Recorded from source

**A 2026 update adds actual binding-kinetic experiments.** Investigators measured DAT-current recovery after inhibitor removal, compared R-modafinil with analogues, and studied dopamine dynamics and cognition in rats. More slowly dissociating analogues such as S-MK-26 and (S,S)-CE-158 performed better on selected outcomes, including tasks impaired by scopolamine. Brain exposure also differed. The findings support investigating residence time, but do not isolate it from every pharmacokinetic difference or show that marketed modafinil has no abuse liability. Findings from these analogues belong to their own records. [Niello et al., 2026](https://doi.org/10.1016/j.neuropharm.2026.110969)

evidence_access

Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.

experimental_model

Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

s-modafinil had radioligand-displacement Ki 2.5 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.

primary_references

R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. | 2012 | DOI 10.1016/j.biopsych.2012.03.022 | PMID 22537794 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/ | https://pubmed.ncbi.nlm.nih.gov/22537794/

source_locator

Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 40–46

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds. · Recorded from source · Recorded from source

| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM | |---|---:|---:| | Racemic modafinil | 13 | 2.3 | | R-modafinil | 4.0 | 0.78 | | S-modafinil | 8.7 | 2.5 | These are reported point estimates, not interchangeable constants. Uptake inhibition and equilibrium binding differ. The racemate's result should not be replaced by a calculated average of its enantiomers. [2012 study, Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/)

evidence_access

Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.

experimental_model

Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

s-modafinil had dopamine uptake IC50 8.7 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.

primary_references

R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. | 2012 | DOI 10.1016/j.biopsych.2012.03.022 | PMID 22537794 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/ | https://pubmed.ncbi.nlm.nih.gov/22537794/

source_locator

Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 40–46

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds. · Recorded from source · Recorded from source

| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM | |---|---:|---:| | Racemic modafinil | 13 | 2.3 | | R-modafinil | 4.0 | 0.78 | | S-modafinil | 8.7 | 2.5 | These are reported point estimates, not interchangeable constants. Uptake inhibition and equilibrium binding differ. The racemate's result should not be replaced by a calculated average of its enantiomers. [2012 study, Table 1](https://pmc.ncbi.nlm.nih.gov/articles/PMC3413742/)

evidence_access

Primary abstract and publisher experimental procedures, results and discussion inspected; no supplementary-data reanalysis.

experimental_model

DAT-current recovery after inhibitor removal; transporter construct details remain in primary paper, not asserted as human clinical kinetics.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

ss-ce-158 was among the more slowly dissociating modafinil analogues in the 2026 DAT-current-recovery experiments; plasma persistence and target residence are separate.

primary_references

Optimizing cognitive enhancement through dopamine transporter modulation. | 2026 | DOI 10.1016/j.neuropharm.2026.110969 | PMID 41980668 | https://doi.org/10.1016/j.neuropharm.2026.110969

source_locator

Reviewed reference lines 67-67; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 67–67

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · DAT-current recovery after inhibitor removal; transporter construct details remain in primary paper, not asserted as human clinical kinetics. · Recorded from source · Recorded from source

**A 2026 update adds actual binding-kinetic experiments.** Investigators measured DAT-current recovery after inhibitor removal, compared R-modafinil with analogues, and studied dopamine dynamics and cognition in rats. More slowly dissociating analogues such as S-MK-26 and (S,S)-CE-158 performed better on selected outcomes, including tasks impaired by scopolamine. Brain exposure also differed. The findings support investigating residence time, but do not isolate it from every pharmacokinetic difference or show that marketed modafinil has no abuse liability. Findings from these analogues belong to their own records. [Niello et al., 2026](https://doi.org/10.1016/j.neuropharm.2026.110969)

evidence_access

Primary indexed abstract checked; full methods and figures not comprehensively reviewed.

experimental_contrast

{"intervention": "Modafinil concentration series", "comparator": "Assay control", "endpoint": "Modafinil inhibited dopamine uptake more potently than norepinephrine uptake in the human-transporter assays.", "effect_direction": "decrease", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human-transporter cell assays; monkey intravenous PET is a separate experiment, not proof of oral-human NET contribution.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

Modafinil inhibited dopamine uptake more potently than norepinephrine uptake in the human-transporter assays.

primary_references

Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. | 2006 | DOI 10.1124/jpet.106.106583 | PMID 16885432 | https://pubmed.ncbi.nlm.nih.gov/16885432/

source_locator

Reviewed reference lines 85-85; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 85–85

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human-transporter cell assays; monkey intravenous PET is a separate experiment, not proof of oral-human NET contribution. · Recorded from source · Recorded from source

A rhesus-monkey PET study detected both DAT and NET occupancy after intravenous modafinil. In human-transporter cell assays, dopamine uptake was inhibited more potently than norepinephrine uptake; serotonin uptake inhibition was much weaker. The same work found no direct TAAR1 activation, but altered phenethylamine responses when TAAR1 was coexpressed with particular transporters. This distinguishes **direct receptor agonism from transporter-dependent modulation**. Monkey intravenous target engagement does not establish the contribution of human NET at oral therapeutic exposure. [Madras et al., 2006](https://pubmed.ncbi.nlm.nih.gov/16885432/)

evidence_access

Primary indexed abstract checked; full methods and figures not comprehensively reviewed.

experimental_contrast

{"intervention": "Oral modafinil", "comparator": "Baseline/placebo comparison", "endpoint": "Separate raclopride PET measurements after oral modafinil supported increased extracellular dopamine; radiotracer displacement is an indirect indicator, not chemical sampling.", "effect_direction": "increase", "combination": "single", "conditions": []} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human PET, ten healthy men, 200 or 400 mg oral exposure.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

Separate raclopride PET measurements after oral modafinil supported increased extracellular dopamine; radiotracer displacement is an indirect indicator, not chemical sampling.

primary_references

Effects of modafinil on dopamine and dopamine transporters in the male human brain: clinical implications. | 2009 | DOI 10.1001/jama.2009.351 | PMID 19293415 | https://pubmed.ncbi.nlm.nih.gov/19293415/

source_locator

Reviewed reference lines 36-36; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 36–36

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human PET, ten healthy men, 200 or 400 mg oral exposure. · Recorded from source · Recorded from source

In a PET study of **10 healthy men**, oral 200 or 400 mg modafinil reduced transporter-radiotracer binding by approximately **54% in caudate, 47% in putamen and 39% in nucleus accumbens**. Separate raclopride measurements supported increased extracellular dopamine. DAT occupancy is not a percentage increase in dopamine; raclopride displacement is an indirect imaging indicator rather than direct chemical sampling. [Volkow et al., 2009](https://pubmed.ncbi.nlm.nih.gov/19293415/)

evidence_access

Full XML obtained; relevant results/methods inspected. Not exhaustive reanalysis of figures or data.

experimental_condition

Same sodium-free buffer without added zinc 10 micromolar added zinc · Zinc(II) ion Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "10 micromolar zinc in sodium-free buffer", "comparator": "Same sodium-free buffer without added zinc", "endpoint": "Adding 10 micromolar zinc in sodium-free binding buffer did not significantly improve modafinil affinity for DAT: Ki approximately 2.96 versus 3.47 micromolar.", "effect_direction": "no_detected_change", "combination": "joint", "conditions": [{"entity_slug": "zinc-ion", "state": "10 micromolar added zinc"}, {"entity_slug": null, "state": "sodium-free buffer"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Human DAT binding assay, sodium-free buffer +/- 10 micromolar zinc; not dietary sodium deficiency or a supplement interaction.

interpretation_status

Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.

limitations

Interpret only within the recorded preparation, exposure and comparator. The complete source passage retains qualifications; unspecified doses/timing have not been extracted here. No clinical efficacy, nutrient deficiency or unique molecular mediation is inferred.

plain_language

Adding 10 micromolar zinc in sodium-free binding buffer did not significantly improve modafinil affinity for DAT: Ki approximately 2.96 versus 3.47 micromolar.

primary_references

The atypical stimulant and nootropic modafinil interacts with the dopamine transporter in a different manner than classical cocaine-like inhibitors. | 2011 | DOI 10.1371/journal.pone.0025790 | PMID 22043293 | https://pmc.ncbi.nlm.nih.gov/articles/PMC3197159/ | https://pubmed.ncbi.nlm.nih.gov/22043293/

source_locator

Reviewed reference lines 56-56; exact primary location described in quoted passage where extracted.

Modafinil: detailed mechanisms of action (reviewed 3 October 2026) · lines 56–56

Original AI-assisted review of primary studies and, where relevant, official regulatory records. Access level is retained per claim. Corrections, null results and unresolved questions remain explicit. Not publisher full text or independent replication. · supports · Human DAT binding assay, sodium-free buffer +/- 10 micromolar zinc; not dietary sodium deficiency or a supplement interaction. · Recorded from source · Recorded from source

A useful **direct nutrient–drug comparison** is contained in that study: in sodium-free binding buffer, adding **10 µM zinc** increased cocaine/methylphenidate binding affinity, but did not significantly improve modafinil affinity. Modafinil Kᵢ was approximately 2.96 µM without zinc and 3.47 µM with it. This is a combined ion-condition experiment, not proof that dietary zinc enhances modafinil or that zinc never affects its response in vivo. Sodium removal is also an assay manipulation, not a model of ordinary dietary sodium deficiency. [Table 2 and methods](https://pmc.ncbi.nlm.nih.gov/articles/PMC3197159/)