{"id":"85d3d05e-c2e9-5e84-b33c-28ad9ba76de8","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:pgp-restricts-ivermectin-brain-entry","predicate":"restricts","statement":"Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"ee8acc94-be25-5589-92fe-4ad454a2bb81","mechanism_event_label":"Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.","subject":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"object":{"id":"e90e793f-7291-5472-bb80-4aae7620d351","slug":"ivermectin-brain-concentration","display_name":"Ivermectin concentration in brain","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ee8acc94-be25-5589-92fe-4ad454a2bb81","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:pgp-restricts-ivermectin-brain-entry-event","event_type":"observed_relationship","label":"Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.","description":"Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"c6139b52-4140-5622-9e33-1f6c6385265d","slug":"abcb1","display_name":"Human P-glycoprotein / ABCB1 / MDR1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e90e793f-7291-5472-bb80-4aae7620d351","slug":"ivermectin-brain-concentration","display_name":"Ivermectin concentration in brain","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a72aed4e-253f-55e0-ae19-59b7141bb026","slug":"mouse-mdr1a-deficiency","display_name":"Mouse mdr1a P-glycoprotein deficiency","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"mdr1a homozygous knockout mice compared with wild type","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ivermectin, described in this report as a centrally neurotoxic pesticide","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"mdr1a homozygous knockout mice compared with wild type","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Mice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vivo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Blood-brain barrier and tissue drug distribution","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"5dc7512c-1249-515d-8cc8-eab36c2db7af","evidence_kind":"source_excerpt","locator":"Lines 57-66","start_line":57,"end_line":66,"excerpt":"## pgp-restricts-ivermectin-brain-entry\nMice lacking the mdr1a P-glycoprotein gene showed about one hundred fold increased sensitivity to ivermectin, and mdr1a P-glycoprotein was the major P-glycoprotein of the blood-brain barrier.\nModel/species: mdr1a homozygous knockout mice compared with wild type\nTissue/system: Blood-brain barrier and tissue drug distribution\nExposure: Ivermectin, described in this report as a centrally neurotoxic pesticide\nRoute: In vivo\nDuration: Not stated here\nLimits: The comparison is a complete gene disruption, which is a stronger manipulation than partial pharmacological inhibition of P-glycoprotein.\nPrimary reference: Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. (1994). https://pubmed.ncbi.nlm.nih.gov/7910522/ DOI: 10.1016/0092-8674(94)90212-7\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"20818ddd-7b37-5226-a24b-7de007e80eb2","stable_key":"import-e0801c92-7fd3-5cb2-82b7-dd82f010f3ed","title":"Ivermectin: mechanism of action across parasite, host barrier and mammalian targets (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of sixteen primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Study-specific citations, concentrations, negative findings and limitations retained. 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