Pyrazolone derivatives

Abstract

In many countries, the pyrazolone derivatives, which include dipyrone, antipyrine, aminopyrine and propyphenazone, are widely used analgesics. Dipyrone, the most widely used pyrazolone, has been the most studied. The pyrazolidine derivatives, phenylbutazone and oxyphenbutazone, which are not generally used for analgesia since they differ from the pyrazolones in terms of efficacy and tolerance, are not discussed in this article. Dipyrone is an inhibitor of cyclo-oxygenase but, unlike aspirin, its effect is rapidly reversible. The inhibition of prostaglandin biosynthesis contributes to the analgesic activity of the pyrazolone derivatives. Peak plasma concentrations of the pyrazolone derivatives generally occur 1 to 1.5 hours after oral administration. Half-lives vary from 1 to 2 hours with propyphenazone, to about 7 hours with dipyrone (2 hours for the active metabolite of dipyrone, 4-methylaminoantipyrine, MAA). Half-life of antipyrine varies considerably between individuals (5 to 35 hours). Unlike the NSAIDs generally, the pyrazolone derivatives antipyrine, aminopyrine and propyphenazone are minimally bound to plasma proteins. The pyrazolones undergo extensive biotransformation, aminopyrine and dipyrone being converted to active metabolites. Dipyrone is the only drug for which results of recent double-blind trials are available. Oral dipyrone has been shown to be more effective than an equal dose of aspirin or paracetamol in alleviating postoperative pain, and intravenous dipyrone 2.5g was similar in efficacy to pethidine 50 mg. In patients with acute ureteral or biliary colic, dipyrone 2.5g intravenously was similar in efficacy to indomethacin 50 mg or pethidine 50 mg. The most frequently reported side effects of the pyrazolone derivatives are skin rashes. Gastrointestinal side effects are rare. Blood dyscrasias, mostly associated with aminopyrine, have received wide attention in the medical literature, but their true incidence with dipyrone is considerably lower than the often quoted incidence for amidopyrine reported more than 30 years ago.