{"id":"03635524-a091-5496-bb2b-8d0be9518cd9","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:modafinil-uptake","predicate":"reported_relationship","statement":"modafinil had dopamine uptake IC50 13 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.","claim_class":"mechanistic","status":"source_recorded","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"29f013a0-b116-53a5-a789-71ed252eec99","mechanism_event_label":"modafinil had dopamine uptake IC50 13 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.","subject":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"object":{"id":"9e5c68df-f041-565a-8c77-b1282ff645eb","slug":"slc6a3","display_name":"Human dopamine transporter / DAT / SLC6A3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"29f013a0-b116-53a5-a789-71ed252eec99","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:modafinil-uptake-event","event_type":"biochemical_relationship","label":"modafinil had dopamine uptake IC50 13 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.","description":"| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM |\n|---|---:|---:|\n| Racemic modafinil | 13 | 2.3 |\n| R-modafinil | 4.0 | 0.78 |\n| S-modafinil | 8.7 | 2.5 |\n\nThese 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/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"role":"tested factor","stoichiometry":null,"state_label":"as reported","sequence_order":0,"notes":""},{"entity":{"id":"9e5c68df-f041-565a-8c77-b1282ff645eb","slug":"slc6a3","display_name":"Human dopamine transporter / DAT / SLC6A3","entity_type_key":"protein"},"role":"measured outcome","stoichiometry":null,"state_label":"not_reported","sequence_order":1,"notes":""},{"entity":{"id":"9cca6209-0603-5ab7-96ad-2f3ae4b772d2","slug":"dopamine","display_name":"Dopamine","entity_type_key":"small_molecule"},"role":"transported substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract and PMC full-text methods, results and Table 1 inspected; XML endpoint unavailable.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived extraction of a fact-checked reference; access is explicit, not independent raw-data verification.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"modafinil had dopamine uptake IC50 13 micromolar in wild-type human DAT expressed in COS-7 cells. Binding and uptake constants are distinct.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"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/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 40-46; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c052fe59-7e54-5a18-8b7a-7f0073b436d2","evidence_kind":"source_excerpt","locator":"Lines 40-46","start_line":40,"end_line":46,"excerpt":"| Compound, wild-type human DAT expressed in COS-7 cells | Dopamine uptake IC₅₀, µM | Radioligand-displacement Kᵢ, µM |\n|---|---:|---:|\n| Racemic modafinil | 13 | 2.3 |\n| R-modafinil | 4.0 | 0.78 |\n| S-modafinil | 8.7 | 2.5 |\n\nThese 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/)","model_system":"Wild-type human DAT expressed in COS-7 cells, 2012 Table 1; point estimates not exposure thresholds.","directness":"reported_statement","verification_status":"source_recorded","notes":"Exact excerpt of the retained AI-assisted reviewed reference; primary sources are cited in primary_references and access scope is retained. Not a verbatim quotation from a primary paper.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"17a64928-eaa2-5117-ba4f-52dcbdf9cc9e","stable_key":"import-6660bba2-4fa0-590a-bf52-9803a24bea9f","title":"Modafinil: detailed mechanisms of action (reviewed 3 October 2026)","document_type":"imported_text","citation_label":"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.","file_path":"","sha256":"006008cb4cfd183dd3b0846d3abc66c8ebf40cf1b6bd1f0bcdb4f4d937a8e115","revision_id":"c85b3e2e-c18a-59fc-9e79-5c375e64d119","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}