{"id":"98b9d971-157c-5104-a6b7-985c2ab6ef7d","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:zinc-dat-null","predicate":"no_detected_change_in_recorded_experiment","statement":"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.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"e1e0d999-f545-5697-95ab-2ada9b07285d","mechanism_event_label":"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.","subject":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"object":{"id":"6065e9bb-c448-5e6a-963f-dd2a658d39e9","slug":"modafinil-human-dat-binding","display_name":"Modafinil affinity for human DAT in binding assays","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e1e0d999-f545-5697-95ab-2ada9b07285d","stable_key":"6660bba2-4fa0-590a-bf52-9803a24bea9f:zinc-dat-null-event","event_type":"experimental_observation","label":"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.","description":"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/)","status":"provisional","compartment":null,"participants":[{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"tested factor","stoichiometry":null,"state_label":"10 micromolar zinc in sodium-free buffer","sequence_order":0,"notes":""},{"entity":{"id":"6065e9bb-c448-5e6a-963f-dd2a658d39e9","slug":"modafinil-human-dat-binding","display_name":"Modafinil affinity for human DAT in binding assays","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"no_detected_change","sequence_order":1,"notes":""},{"entity":{"id":"624e6a4b-f96d-5d12-8206-30d1e1715c26","slug":"modafinil","display_name":"Modafinil","entity_type_key":"drug"},"role":"assayed drug","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9e5c68df-f041-565a-8c77-b1282ff645eb","slug":"slc6a3","display_name":"Human dopamine transporter / DAT / SLC6A3","entity_type_key":"protein"},"role":"binding target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Full XML obtained; relevant results/methods inspected. Not exhaustive reanalysis of figures or data.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_condition","value_text":"10 micromolar added zinc","comparator":"Same sodium-free buffer without added zinc","unit":null,"notes":"Condition belongs to the full experimental contrast; do not separate a joint intervention.","entity":{"slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"}},{"dimension":"experimental_contrast","value_text":"{\"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\"}]}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"Human DAT binding assay, sodium-free buffer +/- 10 micromolar zinc; not dietary sodium deficiency or a supplement interaction.","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":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"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/","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference lines 56-56; exact primary location described in quoted passage where extracted.","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"55f8329f-247b-540e-a0a7-8c096db158e6","evidence_kind":"source_excerpt","locator":"Lines 56-56","start_line":56,"end_line":56,"excerpt":"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/)","model_system":"Human DAT binding assay, sodium-free buffer +/- 10 micromolar zinc; not dietary sodium deficiency or a supplement interaction.","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}