{"id":"631931e1-650f-5053-bf66-91c47ca7ed1c","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-two-antagonists-block-it","predicate":"inhibits","statement":"In rats using the hot plate test the analgesic effect of paracetamol was prevented by two antagonists at cannabinoid CB1 receptors, AM281 and SR141716A, at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210, suggesting that paracetamol-induced antinociception involves the cannabinoid system.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"9d83633c-ca62-5018-bd60-5dbab70914ea","mechanism_event_label":"Two different blockers of the cannabinoid receptor each stopped the painkiller working.","subject":{"id":"717251de-de2d-52ab-9130-ba2dabda79a3","slug":"am251","display_name":"AM251, a cannabinoid receptor 1 antagonist","entity_type_key":"chemical_species"},"object":{"id":"a8d9eb77-f7c5-52c2-8ad5-22547b6917c4","slug":"antinociception-apap","display_name":"Antinociception in thermal, mechanical and chemical pain tests","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9d83633c-ca62-5018-bd60-5dbab70914ea","stable_key":"7de430a5-1a36-5231-b931-35cc01d8f3bf:apap-two-antagonists-block-it-event","event_type":"observed_intervention","label":"Two different blockers of the cannabinoid receptor each stopped the painkiller working.","description":"In rats using the hot plate test the analgesic effect of paracetamol was prevented by two antagonists at cannabinoid CB1 receptors, AM281 and SR141716A, at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210, suggesting that paracetamol-induced antinociception involves the cannabinoid system.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d092243c-94e9-5f03-a406-2fa245f2f4ae","slug":"cnr1","display_name":"Human cannabinoid receptor 1 / CB1 / CNR1","entity_type_key":"protein"},"role":"blocked_receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"a901be21-7915-543c-ac67-c39ef72b0d03","slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"},"role":"affected_drug","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"717251de-de2d-52ab-9130-ba2dabda79a3","slug":"am251","display_name":"AM251, a cannabinoid receptor 1 antagonist","entity_type_key":"chemical_species"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"a8d9eb77-f7c5-52c2-8ad5-22547b6917c4","slug":"antinociception-apap","display_name":"Antinociception in thermal, mechanical and chemical pain tests","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/paracetamol-research/16438952.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8fe3f4535ff4a14c2e417850a583722fc34262e925952ff2fdd9fe244c7e218f\", \"start_char\": 0, \"end_char\": 509, \"text_sha256\": \"8fe3f4535ff4a14c2e417850a583722fc34262e925952ff2fdd9fe244c7e218f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Hot plate test in rats with two cannabinoid receptor antagonists","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Paracetamol with AM281 and SR141716A at doses that prevent the action of a cannabinoid agonist","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A short report with the antagonist doses anchored to a positive control. One pain test in one species.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetaminophen","display_name":"Paracetamol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Two different blockers of the cannabinoid receptor each stopped the painkiller working.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[apap-p16438952] The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. (2006). https://pubmed.ncbi.nlm.nih.gov/16438952/ DOI: 10.1016/j.ejphar.2005.12.015","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Whole animal","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"72f62559-d67d-5e93-9ebf-8e2c0685901b","evidence_kind":"source_excerpt","locator":"Lines 350-361","start_line":350,"end_line":361,"excerpt":"### apap-two-antagonists-block-it\nIn rats using the hot plate test the analgesic effect of paracetamol was prevented by two antagonists at cannabinoid CB1 receptors, AM281 and SR141716A, at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210, suggesting that paracetamol-induced antinociception involves the cannabinoid system.\nCondition category: normal\nnutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404.\nplain_language: Two different blockers of the cannabinoid receptor each stopped the painkiller working.\norganism: Rat\ntissue_or_cell_type: Whole animal\nexperimental_model: Hot plate test in rats with two cannabinoid receptor antagonists\nlimitations: A short report with the antagonist doses anchored to a positive control. One pain test in one species.\nexposure: Paracetamol with AM281 and SR141716A at doses that prevent the action of a cannabinoid agonist\nevidence_span: {\"source_cache\": \"artifacts/paracetamol-research/16438952.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"8fe3f4535ff4a14c2e417850a583722fc34262e925952ff2fdd9fe244c7e218f\", \"start_char\": 0, \"end_char\": 509, \"text_sha256\": \"8fe3f4535ff4a14c2e417850a583722fc34262e925952ff2fdd9fe244c7e218f\"}\n[apap-p16438952] The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. (2006). https://pubmed.ncbi.nlm.nih.gov/16438952/ DOI: 10.1016/j.ejphar.2005.12.015","model_system":"Hot plate test in rats with two cannabinoid receptor antagonists","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. 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