On the mode of action of antiphlogistically active DL-omega-phenyl amino acid esters.
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.
Schewe
C
C
Institute of Biochemistry, Medical School (Charité), Humboldt-University, Berlin, FRG.
Schulz
E
E
Vietinghoff
G
G
Sprung
W D
WD
Kobow
M
M
Loose
S
S
Schewe
T
T
D000596:Amino Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004952:Esters / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects*; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007975:Leukotriene B4 / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011463:Prostaglandins H / Q000096:biosynthesis*; D051381:Rats; D012756:Sheep; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004952:Esters; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D011463:Prostaglandins H; D007975:Leukotriene B4; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D002351:Carrageenan