By a News Reporter-Staff News Editor at Life Science Weekly -- New research on Enzymes and Coenzymes is the subject of a report. According to news reporting from Oporto, Portugal, by NewsRx journalists, research stated, "Etamicastat [®-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride] is a reversible dopamine-beta-hydroxylase inhibitor that decreases norepinephrine levels in sympathetically innervated tissues. After in vivo administration, N-acetylation of etamicastat was found to be a main metabolic pathway."
The news correspondents obtained a quote from the research from the Institute of Pharmacology, "The purpose of the current study was to characterize the N-acetylation of etamicastat by N-acetyltransferases (NAT1 and NAT2) and evaluate potential species differences in etamicastat N-acetylation using a sensitive and specific liquid chromatography-mass spectrometry assay. Marked differences in etamicastat N-acetylation were observed among the laboratory species and humans. After oral administration, the rat, hamster, and human subjects presented the highest rates of etamicastat N-acetylation, whereas almost no acetylation was observed in the mouse, rabbit, minipig, and monkey and no acetylation was observed in the dog. In in vitro studies, rats and humans showed similar acetylation rates, whereas no acetylation was detected in the dog. Studies performed with human recombinant NAT1 4 and NAT2 4 enzymes revealed that both were able to conjugate etamicastat, although at different rates. NAT1 had lower affinity compared with NAT2 (K-m, 124.8 +/- 9.031 mu M and 17.14 +/- 3.577 mu M, respectively). A significant correlation (r(2) = 0.65, P< 0.05) was observed in a comparison of etamicastat N-acetylation by human single-donor enzymes and sulfamethazine, a selective substrate to NAT2. No correlation was observed with p-aminosalicylic acid, a NAT1 selective substrate."
According to the news reporters, the research concluded: "These results suggest that NAT2 and, to a lesser extent, NAT1 contribute to etamicastat N-acetylation. Furthermore, the high interspecies and intraspecies differences in N-acetylation should be taken into consideration when evaluating the in vivo bioavailability of etamicastat."
For more information on this research see: N-Acetylation of Etamicastat, a Reversible Dopamine-beta-Hydroxylase Inhibitor. Drug Metabolism and Disposition, 2013;41(12):2081-2086. Drug Metabolism and Disposition can be contacted at: Amer Soc Pharmacology Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995, USA (see also Enzymes and Coenzymes).
Our news journalists report that additional information may be obtained by contacting A.I. Loureiro, Inst Pharmacol & Therapeut, Fac Med, Oporto, Portugal. Additional authors for this research include C. Fernandes-Lopes, M.J. Bonifacio, L.C. Wright and P. Soares-da-Silva.
Keywords for this news article include: Oporto, Europe, Portugal, Oxidoreductases, Enzymes and Coenzymes, Dopamine beta-Hydroxylase, Mixed Function Oxygenases
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2013, NewsRx LLC