{"id":"8ddd6e66-aa63-5e6e-b3d4-a5c16dd3655d","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-glycine-receptor-activation","predicate":"activates","statement":"Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"24b89330-f3ce-5a98-95eb-4862208e1981","mechanism_event_label":"Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.","subject":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"object":{"id":"b40b5391-68b1-5939-86b2-fa3b7e7681d8","slug":"human-glra1-homomer","display_name":"Human alpha1 homomeric glycine receptor","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"24b89330-f3ce-5a98-95eb-4862208e1981","stable_key":"e0801c92-7fd3-5cb2-82b7-dd82f010f3ed:ivermectin-glycine-receptor-activation-event","event_type":"observed_relationship","label":"Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.","description":"Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"416b9886-c6a5-5526-a8bf-b571a8d418bf","slug":"ivermectin","display_name":"Ivermectin","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b40b5391-68b1-5939-86b2-fa3b7e7681d8","slug":"human-glra1-homomer","display_name":"Human alpha1 homomeric glycine receptor","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Acute and irreversible within the experiment","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":"Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"0.03 micromolar potentiation and higher-concentration irreversible activation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Ivermectin-gated currents showed markedly reduced sensitivity to strychnine, picrotoxin and zinc, so the pharmacology of this activation differs from ordinary glycinergic transmission.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Ivermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Ivermectin, an unconventional agonist of the glycine receptor chloride channel. (2001). https://pubmed.ncbi.nlm.nih.gov/11278873/ DOI: 10.1074/jbc.M011264200","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Inhibitory chloride channel gating","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"51b55d10-0791-5c17-84f0-a624ca1bac65","evidence_kind":"source_excerpt","locator":"Lines 112-121","start_line":112,"end_line":121,"excerpt":"## ivermectin-glycine-receptor-activation\nIvermectin irreversibly activated human alpha1 homomeric and alpha1beta heteromeric glycine receptors at concentrations at or above 0.03 micromolar, through a site that is not the glycine site.\nModel/species: Recombinant human alpha1 homomeric and alpha1beta heteromeric glycine receptors\nTissue/system: Inhibitory chloride channel gating\nExposure: 0.03 micromolar potentiation and higher-concentration irreversible activation\nRoute: In vitro\nDuration: Acute and irreversible within the experiment\nLimits: Ivermectin-gated currents showed markedly reduced sensitivity to strychnine, picrotoxin and zinc, so the pharmacology of this activation differs from ordinary glycinergic transmission.\nPrimary reference: Ivermectin, an unconventional agonist of the glycine receptor chloride channel. (2001). https://pubmed.ncbi.nlm.nih.gov/11278873/ DOI: 10.1074/jbc.M011264200\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. Not publisher full text.","file_path":"","sha256":"c7e1e0201cbd222f0c52b7981f078936ed39b617d747821ed6daa584c2b964a7","revision_id":"56746c3e-cdec-5b8f-a191-425de1a0a7ce","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}