On the mode of action of antiphlogistically active DL-omega-phenyl amino acid esters.

Abstract

DL-omega-phenyl amino acid esters turned out to be inhibitors of the sheep vesicular gland prostaglandin H synthase in addition to their antiphlogistic action on the carrageenan-induced oedema of the rat paw and weak antihistaminic actions. The inhibition of the prostaglandin H synthase was dose-dependent, the inhibitory potencies were however much lower than that of indomethacin. Some but not all derivatives, such as DL-4-amino-4-phenylbutyric acid octyl ester, also caused inhibition of the pure lipoxygenase from rabbit reticulocytes and the conversion of arachidonic acid to leukotriene B4 and 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid by human polymorphonuclear leukocytes as well as inhibition of antigen-induced release of histamine from mast cells of ovalbumin-sensibilized rats. Since no clear relations between the data of the in vitro and in vivo models were obtained, further studies on the pharmacokinetics and possible biotransformations are required.