{"id":"defba50f-5fe3-5a17-a324-b54b7d3d5fa7","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-atenolol-suppression","predicate":"dose_dependently_reduces","statement":"All tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7e9da1ad-25ed-572e-84c4-aa74c3f4813e","mechanism_event_label":"A medicine can weaken the normal secretion signal even when synthetic nutrients are available.","subject":{"id":"5af8304e-4059-5331-88c9-4ecf49ab805f","slug":"atenolol","display_name":"Atenolol","entity_type_key":"small_molecule"},"object":{"id":"3e333fd8-10c9-57be-b97e-af220809ee2b","slug":"nocturnal-melatonin-concentration","display_name":"Nocturnal circulating melatonin concentration","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7e9da1ad-25ed-572e-84c4-aa74c3f4813e","stable_key":"3279ff78-2460-5064-bfc0-3f2987af85a0:melatonin-atenolol-suppression-event","event_type":"observed_intervention","label":"A medicine can weaken the normal secretion signal even when synthetic nutrients are available.","description":"All tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"458438cb-6ce1-5c8f-8bfe-e3d16031b0f0","slug":"adrb1","display_name":"Human beta-1 adrenergic receptor / ADRB1","entity_type_key":"protein"},"role":"blocked_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"role":"measured_hormone","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"5af8304e-4059-5331-88c9-4ecf49ab805f","slug":"atenolol","display_name":"Atenolol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3e333fd8-10c9-57be-b97e-af220809ee2b","slug":"nocturnal-melatonin-concentration","display_name":"Nocturnal circulating melatonin concentration","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/melatonin-research/9406983.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718\", \"start_char\": 0, \"end_char\": 1175, \"text_sha256\": \"7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Randomized single-blind dose-response study","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Atenolol 12.5, 25, 37.5 or 50 mg versus placebo; week washouts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Acute beta1 blockade and small sample. 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(1997). https://pubmed.ncbi.nlm.nih.gov/9406983/ DOI: 10.1111/j.1600-079x.1997.tb00345.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Nocturnal melatonin secretion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"6695ecac-e65f-5585-8e0a-0dfb7edaed72","evidence_kind":"source_excerpt","locator":"Lines 968-979","start_line":968,"end_line":979,"excerpt":"### melatonin-atenolol-suppression\nAll tested atenolol doses reduced nocturnal melatonin relative to placebo, with a dose-dependent pattern.\nCondition category: machinery_impairment\nnutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A medicine can weaken the normal secretion signal even when synthetic nutrients are available.\norganism: Six healthy humans\ntissue_or_cell_type: Nocturnal melatonin secretion\nexperimental_model: Randomized single-blind dose-response study\nlimitations: Acute beta1 blockade and small sample. A lower concentration does not by itself establish symptomatic deficiency or a need for replacement.\nexposure: Atenolol 12.5, 25, 37.5 or 50 mg versus placebo; week washouts\nevidence_span: {\"source_cache\": \"artifacts/melatonin-research/9406983.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718\", \"start_char\": 0, \"end_char\": 1175, \"text_sha256\": \"7d3fe9b237757bb5797ed40bbc26931a04868f9160ea458dd1264671c77e0718\"}\n[melatonin-p9406983] The effect of atenolol, a beta1-adrenergic antagonist, on nocturnal plasma melatonin secretion: evidence for a dose-response relationship in humans. 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