Pharmacological characteristics of metamizole

• Autorzy: Jasiecka A. , Maslanka T. , Jaroszewski J. J.
• Języki publikacji: EN

Abstrakty

EN

Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca²⁺ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole- induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

• Wydawca: -
• Czasopismo: Polish Journal of Veterinary Sciences
• Rocznik: 2014
• Tom: 17
• Numer: 1
• Opis fizyczny: p.207-214,ref.

Twórcy

autor

Jasiecka A.

• Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland

autor

Maslanka T.

• Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland

autor

Jaroszewski J. J.

• Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland

Bibliografia

• Arellano F, Sacristan JA (1990) Metamizole: reassessment of its therapeutic role. Eur J Clin Pharmacol 38: 617-619.
• Bar-Oz B, Clementi M, Di Giantonio E, Greenberg R, Beer M, Merlob P, Arnon J, Ornoy A, Zimmerman DM, Berkovitch M (2005) Metamizol (dipyrone, optalgin) in pregnancy, is it safe? A prospective comparative study. Eur J Obstet Gynecol Reprod Biol 119: 176-179.
• Basak GW, Drozd-Sokołowska J, Wiktor-Jedrzejczak W (2010) Update on the incidence of metamizole sodium- induced blood dyscrasias in Poland. J Int Med Res 38: 1374-1380.
• Batu OS, Erol K (2007) The effects of some nonsteroidal anti-inflammatory drugs on experimental induced gastric ulcers in rats. Inflammopharmacology 15: 260-265.
• Baumgartner CM, Koenighaus H, Ebner JK, Henke J, Schuster T, Erhardt WD (2009) Cardiovascular effects of dipyrone and propofol on hemodynamic function in rabbits. Am J Vet Res 70: 1407-1415.
• Berenguer B, Alarcón de la Lastra C, Moreno FJ, Marttn MJ (2002) Chronic gastric ulcer healing in rats subjected to selective and non-selective cyclooxygenase-2 inhibitors. Eur J Pharmacol 442: 125-135.
• Bigal ME, Bordini CA, Speciali JG (2002) Intravenous dipyrone for the acute treatment of episodic tension-type headache: a randomized, placebo-controlled, double-blind study. Braz J Med Biol Res 35: 1139-1145.
• Biovetalgin, summary of product characteristic. Available from: http://biowet-drwalew.pl/index.php?lang=-pl&module=oferta&page=00&id=15&index=09.
• Botting RM (2000) Mechanism of action of acetaminophen: is there a cyclooxygenase 3? Clin Infect Dis 31: S202- -S210.
• Botting RM (2006) Inhibitors of cyclooxygenases: mechanisms, selectivity and uses. J Physiol Pharmacol 57: S113- -S124.
• Brogden RN (1986) Pyrazolone derivatives. Drugs 32: 60-70.
• Campos C, de Gregorio R, García-Nieto R, Gago F, Ortiz P, Alemany S (1999) Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol 378: 339-347.
• Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL (2002) COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A 99: 13926-13931.
• Chaparro LE, Lezcano W, Alvarez HD, Joaqui W (2012) Analgesic effectiveness of dipyrone (metamizol) for postoperative pain after herniorrhaphy: a randomized, double-blind, dose-response study. Pain Pract 12: 142-147.
• Cohen O, Zylber-Katz E, Caraco Y, Granit L, Levy M (1998) Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone. Eur J Clin Pharmacol 54: 549-553.
• da Silva Dal Pizzol T, Schüler-Faccini L, Mengue SS, Fischer MI (2009) Dipyrone use during pregnancy and adverse perinatal events. Arch Gynecol Obstet 279: 293-297.
• De Souza GE, Cardoso RA, Melo MC, Fabricio AS, Silva VM, Lora M, De Brum-Fernandes AJ, Rae GA, Ferreira SH, Zampronio AR (2002) A comparative study of the antipyretic effects of indomethacin and dipyrone in rats. Inflamm Res 51: 24-32.
• Domínguez-Ramírez AM, Corts-Arroyo AR, Y de la Peña MH, López JR, López-Muñoz FJ (2010) Effect of metamizol on morphine pharmacokinetics and pharmacodynamics after acute and subchronic administration in arthritic rats. Eur J Pharmacol 645: 94-101.
• Drobnik L (2010) Metamizol w uśmierzaniu bólu okołooperacyjnego - współczesne spojrzenie na tradycyjny lek. Anestezjologia i Ratownictwo 4: 40-48.
• Edwards JE, Meseguer F, Faura CC, Moore RA, McQuay HJ (2001) Single-dose dipyrone for acute postoperative pain. Cochrane Database Syst Rev 3: CD003227.
• Escobar W, Ramirez K, Avila C, Limongi R, Vanegas H, Vazquez E (2012) Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur J Pain 16: 676-689.
• Fajt VR (2001) Label and extra label drug use in small ruminants. Vet Clin North Am Food Anim Pract 17: 403-420.
• Garcıa-Martínez JM, Fresno Vara JA, Lastres P, Bernabéu C, Betés PO, Martín-Pérez J (2003) Effect of metamizol on promyelocytic and terminally differentiated granulocytic cells. Comparative analysis with acetylsalicylic acid and diclofenac. Biochem Pharmacol 65: 209-217.
• Gómez E, Blanca-Lopez N, Torres MJ, Requena G, Rondon C, Canto G, Blanca M, Mayorga C (2009) Immunoglobulin E-mediated immediate allergic reactions to dipyrone: value of basophil activation test in the identification of patients. Clin Exp Allergy 39: 1217-1224.
• Gulmez SE, Gurdal H, Tulunay FC (2006) Airway smooth muscle relaxations induced by dipyrone. Pharmacology 78: 202-208.
• Gulmez SE, Celik G, Misirligil Z, Tulunay FC (2007) Dipyrone improves small airway function in asthmatic patients with moderate obstruction. J Investig Allergol Clin Immunol 17: 242-248.
• Hedenmalm K, Spigset O (2002) Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole). Eur J Clin Pharmacol 58: 265-274.
• Hinz B, Cheremina O, Bachmakov J, Renner B, Zolk O, Fromm MF, Brune K (2007) Dipyrone elicits substantial inhibition of peripheral cyclooxygenases in humans: new insights into the pharmacology of an old analgesic. FASEB J 21: 2343-2351.
• Ibanez L, Vidal X, Ballarín E, Laporte JR (2005) Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol 60: 821-829.
• Imagawa VH, Fantoni DT, Tatarunas AC, Mastrocinque S, Almeida TF, Ferreira F, Posso IP (2011) The use of different doses of metamizol for post-operative analgesia in dogs. Vet Anaesth Analg 38: 385-393.
• Jaroszewski JJ, Markiewicz W, Maślanka TS, Skarzyński DJ (2009) Influence of nonsteroidal anti-inflammatory drugs on progesterone production by cultured bovine luteal cells. Pol J Vet Sci 12: 305-310.
• Kanashiro A, Pessini AC, Machado RR, Malvar Ddo C, Aguiar FA, Soares DM, do Vale ML, de Souza GE (2009) Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats. Am J Physiol Regul Integr Comp Physiol 296: R1631- -R1640.
• Levy M, Zylber-Katz E, Rosenkranz B (1995) Clinical pharmacokinetics of dipyrone and its metabolites. Clin Pharmacokinet 28: 216-234.
• López-Muñoz FJ, Godínez-Chaparro B, Huerta-Cruz JC, Guevara-López U, Domínguez-Ramtrez AM, Cortés-Arroyo AR (2008) The antinociceptive efficacy of morphine, metamizol, or their combination in an experimental rat model with different levels of inflammatory pain. Pharmacol Biochem Behav 91: 196-201.
• Maddison JE, Page SW, Church D (2008) Small animal clinical pharmacology. 2nd ed., Elsevier Health Sciences, p 298.
• Maj S, Lis Y (2002) The incidence of metamizole sodium- induced agranulocytosis in Poland. J Int Med Res 30: 488-495.
• Malvar Ddo C, Soares DM, Fabrício AS, Kanashiro A, Machado RR, Figueiredo MJ, Rae GA, de Souza GE (2011) The antipyretic effect of dipyrone is unrelated to inhibition of PGE(2) synthesis in the hypothalamus. Br J Pharmacol 162: 1401-1409.
• Muñoz J, Navarro C, Noriega V, Pinardi G, Sierralta F, Prieto JC, Miranda HF (2010) Synergism between COX-3 inhibitors in two animal models of pain. Inflammopharmacology 18: 65-71.
• Nikolova I, Tencheva J, Voinikov J, Petkova V, Benbasat N, Danchev N (2012) Metamizole: A review profile of A well-known` forgotten’ drug. Part I: Pharmaceutical and nonclinical profile. Biotechnol & Biotechnol Eq 26: 3329- -3337.
• Oberhofer D, Skok J, Nesek-Adam V (2005) Intravenous ketoprofen in postoperative pain treatment after major abdominal surgery. World J Surg 29: 446-449.
• Pessini AC, Santos DR, Arantes EC, Souza GE (2006) Mediators involved in the febrile response induced by Tityus serrulatus scorpion venom in rats. Toxicon 48: 556-566.
• Pierre SC, Schmidt R, Brenneis C, Michaelis M, Geisslinger G, Scholich K (2007) Inhibition of cyclooxygenases by dipyrone. Br J Pharmacol 151: 494-503.
• Pyralgin, summary of product characteristic. Available from: http://leki-informacje.pl/jamnik/img/galeriaplikow/2/pyralgin-roztwor-05-mgml-2012.pdf.
• Rogosch T, Sinning C, Podlewski A, Watzer B, Schlosburg J, Lichtman AH, Cascio MG, Bisogno T, Di Marzo V, Nusing R, Imming P (2012) Novel bioactive metabolites of dipyrone (metamizol). Bioorg Med Chem 20: 101-107.
• Rutkowska M, Jamontt J (2005) Rola układu kannabinoidowego w fizjologii i patofizjologii ośrodkowego układu nerwowego. Adv Clin Exp Med 14: 1243-1252.
• Sánchez S, Alarcón de la Lastra C, Ortiz P, Motilva V, Martín MJ (2002) Gastrointestinal tolerability of metamizol, acetaminophen, and diclofenac in subchronic treatment in rats. Dig Dis Sci 47: 2791-2798.
• Schug SA, Manopas A (2007) Update on the role of non-opioids for postoperative pain treatment. Best Pract Res Clin Anaesthesiol 21: 15-30.
• Shimada SG, Otterness IG, Stitt JT (1994) A study of the mechanism of action of the mild analgesic dipyrone. Agents Actions 41: 188-192.
• Smith GW, Davis JL, Tell LA, Webb AI, Riviere JE (2008) Extralabel use of nonsteroidal anti-inflammatory drugs in cattle. J Am Vet Med Assoc 232: 697-701.
• Taylor J, Mellstrom B, Fernaud I, Naranjo JR (1998) Metamizol potentiates morphine effects on visceral pain and evoked c-Fos immunoreactivity in spinal cord. Eur J Pharmacol 351: 39-47.
• Tortorici V, Vanegas H (2000) Opioid tolerance induced by metamizol (dipyrone) microinjections into the periaqueductal grey of rats. Eur J Neurosci 12: 4074-4080
• Uetrecht JP, Ma HM, MacKnight E, McClelland R (1995) Oxidation of aminopyrine by hypochlorite to a reactive dication: possible implications for aminopyrine-induced agranulocytosis. Chem Res Toxicol 8: 226-233.
• Vazquez E, Hernandez N, Escobar W, Vanegas H (2005) Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats. Brain Res 1048: 211-217.
• Vlahov V, Badian M, Verho M, Bacracheva N (1990) Pharmacokinetics of metamizol metabolites in healthy subjects after a single oral dose of metamizol sodium. Eur J Clin Pharmacol 38: 61-65.
• Weithmann KU, Alpermann HG (1985) Biochemical and pharmacological effects of dipyrone and its metabolites in model systems related to arachidonic acid cascade. Arzneimittelforschung 35: 947-952.
• Wessel JC, Matyja M, Neugebauer M, Kiefer H, Daldrup T, Tarbah FA, Weber H (2006) Characterization of oxalic acid derivatives as new metabolites of metamizol (dipyrone) in incubated hen’s egg and human. Eur J Pharm Sci 28: 15-25.
• Żukowski M, Kotfis K (2009) Safety of metamizole and paracetamol for acute pain treatment. Anestezjol Intens Ter 41: 170-175.

Identyfikatory

DOI

10.2478/pjvs-2014-0030