Dipyrone / metamizole

Where it participates (unsigned role)

1. A third distinct cyclooxygenase isozyme, COX-3, made from the cyclooxygenase-1 gene but retaining intron 1 in its messenger RNA, was described as expressed in canine cerebral cortex and as an approximately 5.2 kilobase transcript most abundant in human cerebral cortex and heart, the retained intron introducing an insertion of 30 to 34 amino acids into the hydrophobic signal peptide; canine COX-3 expressed in insect cells possessed glycosylation-dependent cyclooxygenase activity and was selectively inhibited by analgesic and antipyretic drugs such as acetaminophen, phenacetin, antipyrine and dipyrone, so that inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.

   Paracetamol → COX-3 / COX-1b, a cyclooxygenase-1 transcript retaining intron 1 source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/paracetamol-research/12242329.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c00962f9e58da9af386335ac3312d5c260d637270d80481a6f55d0ebec67a78", "start_char": 0, "end_char": 1711, "text_sha256": "0c00962f9e58da9af386335ac3312d5c260d637270d80481a6f55d0ebec67a78"}

   experimental_model

   Cloning and expression of cyclooxygenase-1-derived transcripts from canine cerebral cortex in insect cells

   exposure

   Canine COX-3 compared with murine cyclooxygenase-1 and -2 against acetaminophen, phenacetin, antipyrine and dipyrone

   limitations

   The paper that proposed the answer. Its activity data are for the canine protein expressed in insect cells; the human claim is about messenger RNA abundance, not about an active protein.

   nutrient_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. · Paracetamol

   organism

   Dog and human

   plain_language

   A third form of the enzyme was reported in dog brain, and it was the one this drug blocked.

   primary_references

   [apap-p12242329] COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. (2002). https://pubmed.ncbi.nlm.nih.gov/12242329/ DOI: 10.1073/pnas.162468699

   tissue_or_cell_type

   Cerebral cortex

   Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 194–205

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and expression of cyclooxygenase-1-derived transcripts from canine cerebral cortex in insect cells · source_derived_draft · unverified_draft

   ### apap-cox3-proposed A third distinct cyclooxygenase isozyme, COX-3, made from the cyclooxygenase-1 gene but retaining intron 1 in its messenger RNA, was described as expressed in canine cerebral cortex and as an approximately 5.2 kilobase transcript most abundant in human cerebral cortex and heart, the retained intron introducing an insertion of 30 to 34 amino acids into the hydrophobic signal peptide; canine COX-3 expressed in insect cells possessed glycosylation-dependent cyclooxygenase activity and was selectively inhibited by analgesic and antipyretic drugs such as acetaminophen, phenacetin, antipyrine and dipyrone, so that inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever. Condition category: normal nutrient_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. plain_language: A third form of the enzyme was reported in dog brain, and it was the one this drug blocked. organism: Dog and human tissue_or_cell_type: Cerebral cortex experimental_model: Cloning and expression of cyclooxygenase-1-derived transcripts from canine cerebral cortex in insect cells limitations: The paper that proposed the answer. Its activity data are for the canine protein expressed in insect cells; the human claim is about messenger RNA abundance, not about an active protein. exposure: Canine COX-3 compared with murine cyclooxygenase-1 and -2 against acetaminophen, phenacetin, antipyrine and dipyrone evidence_span: {"source_cache": "artifacts/paracetamol-research/12242329.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c00962f9e58da9af386335ac3312d5c260d637270d80481a6f55d0ebec67a78", "start_char": 0, "end_char": 1711, "text_sha256": "0c00962f9e58da9af386335ac3312d5c260d637270d80481a6f55d0ebec67a78"} [apap-p12242329] COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. (2002). https://pubmed.ncbi.nlm.nih.gov/12242329/ DOI: 10.1073/pnas.162468699

   Complete structured claim and evidence

2. Of 237 challenges with various non-steroidal anti-inflammatory drugs and paracetamol in 101 intolerant patients, 19 challenges were positive and 2 patients developed anaphylactic shock, with a ratio of positive to total challenges of 7 of 83 for paracetamol, 2 of 49 for imidazole-hydroxybenzoate and 0 of 30 for nimesulide, and the authors conclude that a positive history of intolerance to a given drug is sufficient reason to contraindicate its use even for diagnostic challenge, which should be restricted to assessing tolerability of alternatives.

   Paracetamol → Urticaria and angioedema source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/paracetamol-research/7506185.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f", "start_char": 0, "end_char": 1590, "text_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f"}

   experimental_model

   Oral challenge series in 112 and then 284 patients intolerant of non-steroidal anti-inflammatory drugs

   exposure

   Challenges with aspirin, dipyrone, paracetamol, imidazole-hydroxybenzoate and nimesulide

   limitations

   Provides the denominator that the case reports lack, and records two anaphylactic shocks during challenge, which is why the authors restrict the procedure.

   nutrient_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. · Paracetamol

   organism

   Human

   plain_language

   About one in twelve challenges with paracetamol was positive in people already intolerant of these drugs.

   primary_references

   [apap-p7506185] Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents. (1993). https://pubmed.ncbi.nlm.nih.gov/7506185/ DOI: 10.2165/00003495-199300461-00065

   tissue_or_cell_type

   Whole body

   Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 480–491

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral challenge series in 112 and then 284 patients intolerant of non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

   ### apap-seven-in-eighty-three Of 237 challenges with various non-steroidal anti-inflammatory drugs and paracetamol in 101 intolerant patients, 19 challenges were positive and 2 patients developed anaphylactic shock, with a ratio of positive to total challenges of 7 of 83 for paracetamol, 2 of 49 for imidazole-hydroxybenzoate and 0 of 30 for nimesulide, and the authors conclude that a positive history of intolerance to a given drug is sufficient reason to contraindicate its use even for diagnostic challenge, which should be restricted to assessing tolerability of alternatives. Condition category: normal nutrient_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. plain_language: About one in twelve challenges with paracetamol was positive in people already intolerant of these drugs. organism: Human tissue_or_cell_type: Whole body experimental_model: Oral challenge series in 112 and then 284 patients intolerant of non-steroidal anti-inflammatory drugs limitations: Provides the denominator that the case reports lack, and records two anaphylactic shocks during challenge, which is why the authors restrict the procedure. exposure: Challenges with aspirin, dipyrone, paracetamol, imidazole-hydroxybenzoate and nimesulide evidence_span: {"source_cache": "artifacts/paracetamol-research/7506185.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f", "start_char": 0, "end_char": 1590, "text_sha256": "b38b08631ecb8137b8297b631b8dab0a4378d5445e29c557e3586b546e0e874f"} [apap-p7506185] Oral challenge with alternative nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol in patients intolerant to these agents. (1993). https://pubmed.ncbi.nlm.nih.gov/7506185/ DOI: 10.2165/00003495-199300461-00065

   Complete structured claim and evidence