Antiallergic activity and mode of action of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3- pyridyl)acrylamide in experimental animals.
Antiallergic effects of AL-3264 (N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3- pyridyl)acrylamide, CAS 118420-47-6) were compared with those of ketotifen, oxatomide, azelastine and tranilast in experimental animals. AL-3264 inhibited passive cutaneous anaphylaxis (PCA) in rats with an ED50 value of 6.1 mg/kg p.o. In inhibiting PCA, AL-3264 was the most potent among the antiallergic drugs examined. The anti-PCA effect of AL-3264 was long-lasting. Tolerance was not produced by repeated administration of AL-3264. AL-3264 inhibited antigen-induced bronchoconstriction in actively sensitized rats and in passively sensitized guinea pigs, with ED50 values of 14.5 and 0.44 mg/kg p.o., respectively. In the in vitro experiments, AL-3264 inhibited 5-lipoxygenase activity of guinea pig leukocytes with an IC50 value of 4.9 mumol/l, being the most potent among antiallergic drugs examined, and suppressed the antigen-induced histamine release from rat peritoneal mast cells with an IC50 value of 12.2 mumol/l. AL-3264 antagonized histamine-induced contractions in isolated guinea pig trachea with an IC50 value of 0.16 mumol/l. These results suggest that AL-3264 is an orally active, potent and long-lasting antiallergic compound which inhibits 5-lipoxygenase activity, histamine release and histamine H1 receptors at the similar concentrations.
Ishii
K
K
Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd, Suital Osaka, Japan.
Yakuo
I
I
Seto
Y
Y
Kita
A
A
Nakamura
H
H
Nishikawa
Y
Y
D000178:Acrylamides / Q000627:therapeutic use*; D000818:Animals; D000941:Antigens / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects
D000178:Acrylamides; D000941:Antigens; D006633:Histamine Antagonists; D016859:Lipoxygenase Inhibitors; D010879:Piperazines; C080363:AL 3264