title: Effect of novel anti-inflammatory ethanolamine derivatives with antioxidant properties on drug metabolising enzymes.
abstract: The influence of four ethanolamine derivatives with anti-inflammatory and antioxidant activity on the in vitro aminopyrine N-demethylation was studied. It was found that these compounds inhibit the N-demethylation of aminopyrine. 1-Cyclohexyl-5-(2-hydroxy-ethylamino)-pentan-2-one (compound 4), possessing the highest inhibitory activity and found earlier to be a potent anti-inflammatory agent, is further tested in vivo on zoxazolamine-induced paralysis, after a single administration to rats, and on aminopyrine N-demethylation, rat hepatic total cytochrome P450 and protein (postmitochondrial and microsomal) content, after a prolonged treatment. It was found that the examined compound had no significant influence on the above biotransformations, however, it could decrease the catalytically active hepatic cytochrome P450 content. These results, considered together with some structural and physicochemical properties of the compound, indicate that this compound may act as a CYP2D6 substrate.
mesh_terms: D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009125:Muscle Relaxants, Central / Q000037:antagonists & inhibitors / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010243:Paralysis / Q000139:chemically induced / Q000188:drug therapy; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015049:Zoxazolamine / Q000037:antagonists & inhibitors / Q000633:toxicity
chemical_list: D000975:Antioxidants; D004983:Ethanolamines; D009125:Muscle Relaxants, Central; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D015049:Zoxazolamine; D006899:Mixed Function Oxygenases; D000633:Aminopyrine N-Demethylase