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HOME >> API >> API List 2 >> Metamizol Magnesium >> Drug Description

DRUG DESCRIPTION
Metamizol Magnesium CAS No. 6150-97-6

Metamizol  is hydrolyzed in the gastrointestinal tract to the pharmacologically active metabolite 4-methyl-amino-antipyrine (4-MAA), which is transformed by both, oxidation to 4-formyl-amino-antipyrine (4-FAA) and demethylation to 4-amino-antipyrine (4-AA). 4-AA is acetylated to 4-acetyl-amino-antipyrine (4-AcAA). The aim of the present study was to investigate whether cimetidine will alter the pharmacokinetics of the metabolites of metamizol due to cimetidine-induced inhibition of the metabolic transformation of 4-MAA. The study was carried out in 12 patients with duodenal ulcer treated with cimetidine 1,000 mg daily over 20 days. A single oral dose of metamizol 1,500 mg was administered 2 days prior to commencement of cimetidine therapy to all patients. Two further doses of 750 and 1,500 mg of metamizol were given in a randomized order on days 8 and 13 during cimetidine treatment. Blood samples for determination of metamizol metabolites were drown over 48 hours post dose. Drug assays for metamizol metabolites and cimetidine were performed using HPLC methods. The patients were phenotyped for CYP2D6 and acetylation polymorphism. The results revealed that cimetidine interacted with 4-MAA by increasing the systemic availability, prolonging the elimination half-life and decreasing the systemic clearance of 4-MAA, whereas the renal clearances of 4-MAA remained unchanged. Consistent with cimetidine-induced changes in the oxidation of 4-MAA to 4-FAA, as well as in the demethylation of 4-MAA to 4-AA, were the decreased rates of production and the lower maximum concentrations of 4-FAA and 4-AA when metamizol was administered during cimetidine treatment (p < 0.05). No correlation was found between the decrease in the production rates of 4-FAA induced by cimetidine and the hydroxylation abilities of the patients, this suggesting that CYP2D6 is not involved in the metabolism of 4-MAA to 4-FAA. The acetylation of 4-AA to 4-AcAA was not affected by cimetidine. Cimetidine produced an increase not proportional to the dose in the systemic availability only of 4-MAA, whereas the kinetics of the other metabolites changed proportionally to the increasing dose of metamizol.

Metamizol Magnesium is a white, crystalline substance that is freely soluble in water. It differs chemically from the drugs of the thiouracil series primarily because it has a 5- instead of a 6-membered ring. Each tablet contains 5 or 10 mg (43.8 or 87.6 µmol) Metamizol Magnesium , an orally administered antithyroid drug.

Each tablet also contains lactose monohydrate, magnesium stearate, starch (corn), pregelatinized starch and talc.

Antispasmodic drugs have been used to treat stomach cramps. Traditionally, they were used to treat stomach ulcers, but for this purpose they have largely been replaced by the acid inhibiting compoundsa, the H-2 receptor blockers such as cimetidine and ranitidine and the proton pump inhibtors such as omeprazole, lansoprazole and rabetazole.

Most of the drugs used for this purpose as "anti-cholinergics", since they counteract the effects of the neurohormone acetylcholine. Some of these drugs are derived from the plant belladonna, also known as Deadly Nightshade. There is also a group of drugs with similar activity, but not taken from plant sources. The anticholingergics decrease both the movements of the stomach and intestine, and also the secretions of stomach acid and digestive enzymes. They may be used for other purposes including treatment of Parkinson's Disease, and bladder urgency. Because these drugs inhibit secretions, they cause dry mouth and dry eyes because of reduced salivation and tearing. Dicyclomine is an antispasmodic with very lettle effect on secretions. It is used to treat irritable bowel syndrome.

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