Metamizol: the pathway in the body
This page shows the biochemical pathway of the active substance Metamizol: where it arrives in the body, where it acts and which steps are affected by that. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.
In brief
Metamizole is a pyrazolone and not yet active itself. In the body it breaks down without an enzyme into 4-methylaminoantipyrine, which acts on the haem iron of cyclooxygenase. Described is a redirection of the formation rather than a full stop.
What this is about
Metamizole is a prodrug: what is swallowed is not yet the form that acts. Three things set its path apart from that of other inhibitors of cyclooxygenase:
- The breakdown into the active form needs no enzyme. In water, metamizole falls apart by itself into 4-methylaminoantipyrine (MAA); only this molecule passes into the blood.
- The further conversion runs via CYP enzymes and via N-acetyltransferase 2. How fast it runs is laid down in the genes and differs from person to person.
- At the enzyme, MAA does not act in the channel for the fatty acid. It forms firm complexes with the haem and changes the oxidation state of the iron that starts the reaction of cyclooxygenase.
The mechanism is not conclusively settled. The reviews describe that the breakdown products redirect the formation of the prostaglandins rather than stopping it entirely, and they name further points of attack in the nervous system besides cyclooxygenase; what share these have is open. A nutrient whose absorption this substance alters is not described — what is touched is the path of arachidonic acid and the haem iron of the enzyme that converts it.
What this means in an individual case depends on many things and belongs in a conversation with a doctor or health practitioner.
Swipe the graphic sideways
The pathway step by step
- Metamizole → 4-Methylaminoantipyrine · Water Even before absorption, metamizole breaks down in water into 4-methylaminoantipyrine, MAA for short. This breakdown needs no enzyme; it runs by itself. Only MAA passes into the blood. Source 1, 2
- 4-Methylaminoantipyrine → 4-Aminoantipyrine CYP2C19 In the liver CYP2C19 removes the methyl group from MAA; 4-aminoantipyrine (AA) arises. Another part of the MAA is converted into 4-formylaminoantipyrine, an end product. Source 1, 4
- 4-Aminoantipyrine → 4-Acetylaminoantipyrine NAT2 · Acetyl-CoA N-acetyltransferase 2 attaches an acetyl group to AA; it comes from acetyl-CoA. How fast this step runs is laid down in the genes and differs from person to person. Source 1, 4, 5
- 4-Acetylaminoantipyrine → Excretion The four breakdown products leave the body mostly in the urine. The unchanged parent substance is practically undetectable in the blood. Source 1
- In the cell membrane → Free arachidonic acid cPLA2 · Calcium When calcium inside the cell rises, the phospholipase cPLA2 moves to the membrane and cuts arachidonic acid out. Only as a free molecule is it converted further. Source 7
- Free arachidonic acid → PGH₂ COX-1 and COX-2 · Haem iron, Oxygen Cyclooxygenase adds oxygen and forms a ring; PGG₂ arises. The peroxidase part of the same enzyme, a haem with iron, turns it into PGH₂ — the precursor of the prostaglandins and of thromboxane. Source 6, 3
- PGH₂ → Prostaglandin E₂ PGE synthases · Glutathione Tissue-own synthases make the individual prostaglandins out of PGH₂. The microsomal PGE synthase-1 needs glutathione for this. Source 8
- PGH₂ → Thromboxane A₂ Thromboxane synthase In blood platelets the thromboxane synthase converts PGH₂ into thromboxane A₂. There this path runs via COX-1. Source 6
What this active substance affects
- Iron — The active breakdown products bind the haem of cyclooxygenase and turn its Fe³⁺ into Fe²⁺ Source 3, 6
- Arachidonic acid — Starting material of cyclooxygenase; via PGH₂ it gives rise to the prostaglandins and to thromboxane Source 6, 7
What takes part in these steps
- Calcium — When it rises inside the cell, the phospholipase cPLA2 moves to the membrane and frees arachidonic acid Source 7
- Glutathione — The microsomal PGE synthase-1 needs glutathione to convert PGH₂ into prostaglandin E₂ Source 8
- Linoleic acid — Omega-6 fatty acid from food, from which arachidonic acid arises over several steps Source 9
- Acetyl-CoA — Supplies N-acetyltransferase 2 with the acetyl group it attaches to 4-aminoantipyrine Source 5, 1
What a review brings together
There is no US prescribing information for metamizole: the substance is not approved as a medicine in the United States, and DailyMed lists it only as a raw material. The figures therefore come from a systematic review with meta-analysis — 79 trials with almost 4,000 adults who each received the substance for less than two weeks. That review does not count individual complaints; it only compares how often adverse events were reported in total.
How to read the table: it counts no individual complaints but compares groups. Each row states what the comparison was against and how it turned out. There is therefore no separate column for a placebo — the placebo is a row here. And “no difference found” does not mean “no difference present”: with this number of participants, rare events stay invisible.
| Compared with | Adverse events in total | |
|---|---|---|
| Placebo | no difference found | |
| Paracetamol | no difference found | |
| Non-steroidal anti-inflammatory drugs | no difference found | |
| Opioids | fewer on metamizole (ratio of frequencies 0.79) | |
| Serious events, all comparisons | only few reported, no difference | |
| Agranulocytosis or deaths | not reported in these trials |
The review records that the trials assessed were mostly short and the reports of mediocre quality; for longer use, informative trials are missing. As the most severe reaction described, the reviews name agranulocytosis, a steep fall in certain white blood cells. It did not occur in the trials assessed; how common it is cannot be derived from this.
Sources
- Levy M, Zylber-Katz E, Rosenkranz B. Clinical pharmacokinetics of dipyrone and its metabolites. Clin Pharmacokinet 1995 · PubMed 7758252
- Jasiecka A, Maślanka T, Jaroszewski JJ. Pharmacological characteristics of metamizole. Pol J Vet Sci 2014 · PubMed 24724493
- Pierre SC, Schmidt R et al. Inhibition of cyclooxygenases by dipyrone. Br J Pharmacol 2007 · PubMed 17435797
- Martínez C, Andreu I et al. Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole. Biochem Pharmacol 2014 · PubMed 25241292
- Hein DW, Millner LM. Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review. Expert Opin Drug Metab Toxicol 2021 · PubMed 33094670
- Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000 · PubMed 10966456
- Leslie CC. Regulation of the specific release of arachidonic acid by cytosolic phospholipase A2. Prostaglandins Leukot Essent Fatty Acids 2004 · PubMed 15041029
- Samuelsson B, Morgenstern R, Jakobsson PJ. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 2007 · PubMed 17878511
- Brenna JT, Kothapalli KSD. New understandings of the pathway of long-chain polyunsaturated fatty acid biosynthesis. Curr Opin Clin Nutr Metab Care 2022 · PubMed 34937850
- Kötter T, da Costa BR et al. Metamizole-associated adverse events: a systematic review and meta-analysis. PLoS One 2015 · PubMed 25875821
Related pathways
- Ibuprofen — in the cell membrane
As of 2026-09-25. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
Legal notice
Privacy policy
All biomarkers