alexa Abstract | Study on the Relationship between Genetic Polymorphisms of Cytochrome P450 and effects of Dipyrone in dental pain

Journal of Chemical and Pharmaceutical Research
Open Access

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Original Articles Open Access

Abstract

Dipyrone is a non-steroidal anti-inflammatory drug (NSAID), commonly used in the past as a powerful painkiller and fever reducer. It is better known under the brand names Neo-Melubrina®,Analgin®, and Novalgin®. Because of the risk of serious adverse effects, its use is justified only in serious situations where no alternative is available or suitable. Dipyrone is a widely used well tolerated analgesic drug which is how-ever compromised by agranulocytosis as adverse effect. Subsequent to no enzymatic hydrolysis, primary metabolic step is Ndemethylation of 4-meth-ylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800 and 1200 μmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (Quinidine), CYP2C19 (omeprazole,CYP2C9 (sulphaphenazole) and CYP1A1 (alpha -naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0. The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearance of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6 and 1A2 respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). The enzyme CYP2C19 apparently has an important role in N-demethylation of 4- methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis. And the Dipyrone is best dental pain because inhibitor the COX in brine

To read the full article Peer-reviewed Article PDF image

Author(s): Salem O Ali Abdalla Thabet H Nagah Ashraf F Alzalitni and Fathiya Asteal

Keywords

Dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, Enzyme CYP2C19, Genetic Polymorphisms

 
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords