Metamizole

The second group of non-opioid analgesics, which are not classified as NSAIDs, consists of substances that lack anti-inflammatory properties, such as phenazones, metamizole (dipyrone) and paracetamol. Their molecules are neutral or weakly basic, have no hydrophilic... 

C18H17N3O 83-17-0) see Metamizole sodium l-(benzylidenamino)-2,4-imidazolidinedione (CK1H9N3O2 2827-57-8) see Azimilide hydrochloride... 

Ci4HijIN,02 92254-87-0) see Azimilide hydrochloride 4-benzylidenemethylammonio-2,3-dimethyl-l-phenyl-5-A -pyrazolone methyl sulfate (C20H23N3O5S) see Metamizole sodium... 

Irreversible reaction of [18] iodine with acetylsalicylic acid, aethaverine, amidopyrine, ascorbic acid, benzo-caine, quinine, dihydrocodeine, fluorescein, glycine, hydrocortisone acetate, isoni-azid, metamizole, papaverine, paracetamol, phenacetin, phenol-phthalein, piperazine, resorcinol, salicylic acid, salicylamide, sulfaguanidine, thymol, triethanolamine, tris buffer detection by reaction chromatography... 

Metamizole sodium Methamizole sodium, l-phenyl-2,3-dimethyl-4-methylaminopyra-zolone-5-A -sodium methansulfonate (3.2.16), is synthesized in a multi-stage synthesis from acetoacetic ester and phenylhydrazine. Their reaction leads to the formation of 1-phenyl-3-methylpyrazolone-5 (3.2.9). Methylation of this product with methyl iodide gives 1-phenyl-... 

Little information is available regarding tissue distribution or metabolic products of nonsteroidal anti-inflammatory drugs in cattle. The early synthetic compounds were simple derivatives either of salicylic acid such as acetylsalicylic acid and methylsalicylic acid, or of pyrazolone such as metamizole, oxyphenbuta-zone, phenylbutazone, propylphenazone, and suxibuzone. Modern nonsteroidal anti-inflammatory drugs are derivatives either of anthranilic acid such as dido-... 

Metamizole, also known as dipyrone, is a pyrazolone derivative. Metami-zole is administered by intramuscular or intravenous routes to cattle, pigs, sheep, and goats at dosages in the range 15-50 mg/kg bw as an adjunct to therapy in many inflammatory conditions of the musculoskeletal and locomotor systems. 

It is rapidly and almost completely absorbed after oral administration to humans and laboratory animals. It is extensively metabolized to a variety of metabolites, none of which is significantly bound to plasma proteins. After intravenous administration to humans, unmetabolized metamizole is rapidly undetectable in plasma, the majority of the administered dose being excreted in urine. Pharmacological studies in rats showed that 4-methylaminoantipyrin, 4-amino-antipyrin, 4-formylaminoantipyrin, and 4-acetylaminoantipyrin constitute all major metabolites of metamizole. 

Following administration of metamizole to pigs, catde, and lactating cows at or above the recommended therapeutic dosages, all muscle, liver and kidney samples contained residues of the 4-methylaminoantipyrin metabolite well below the detection limit of 100 ppb at all time points. 

Clinical use Metamizol is the water-soluble sodium sulfonate of amidopyrine. After oral administration it is rapidly hydrolyzed to the active 4-methyl-amino-antipyrine and metabolized to various metabolites (Levy et al., 1995 scheme 47). Metamizol has strong analgesic, spasmolytic and antipyretic action, but no anti-inflammatory properties. The exact mechanism of action is unknown but may include inhibition of prostaglandin synthesis. Inhibition of both COX isoenzymes has been demonstrated, although only in extremely high concentrations, thus questioning the relevance of this activity. 

Metamizol is used for the treatment of medium to severe pain, often in combination with opioids, for fever reduction and for the treatment of colic pain. It is given by mouth in doses of 500 mg up to 4 g daily, and by intravenous or rectal routes. 

Scheme 47 Metabolic pathway of metamizol (Weithmann and Alpermann, 1983)...

Metamizol is relatively free of acute side-effects but in rare cases may induce severe and life-threatening allergic reactions such as agranulocytosis, allergic skin reactions and allergic shock. Therefore, the compound is not used in the UK, US or Scandinavian countries. 

A number of muscarinic agonists and antagonists are launched or in clinical trials, especially as antiemetics (e.g. scopolamine), as treatment for urinary incontinence (e.g. tolterodine), glaucoma (pilocarpine), and airway diseases (e.g. ipratropium bromide), but, to the best of our knowledge, only few are used as adjuvants in analgesic compositions, e.g. tiemonium iodide which is used in various combinations with analgesics like paracetamol or metamizole (Coffalon , Visceralgine ). 

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