[Pharmacological profiles of F-1322, a novel anti-asthmatic agent. (1). Mechanisms of action].
The pharmacological effects of N-[2-(4-(benzhydryloxy)piperidino)ethyl]-3-hydroxy-5-(3-pyridyl methoxy)-2- naphthamide (F-1322), a novel anti-asthmatic agent, was investigated in vitro. The results obtained were as follows: 1) In the isolated trachea of guinea pigs, F-1322 showed a markedly potent antagonistic action against the contraction induced by histamine, while it had little or no effect on 5-hydroxytryptamine-, acetylcholine-, leukotriene D4- or U-46619-induced contractions. 2) In rabbit platelets, F-1322 did not affect the platelet aggregation induced by platelet activating factor. 3) F-1322 significantly inhibited the thromboxane (TX) A2 synthetase (IC50 value: 1.7 x 10(-8) M) and 5-lipoxygenase (IC50 value: 9 x 10(-7) M) activities. 4) F-1322 had no effect on phospholipase A2, cyclooxygenase, Ca2+/calmodulin-dependent phosphodiesterase and phosphodiesterase activities. These in vitro studies suggest that the anti-asthmatic action of F-1322 is associated with histamine antagonism and an inhibitory action on TXA2 synthetase and 5-lipoxygenase activities.
Lee
B
B
Pharmaceuticals Research Laboratories, Fujirebio, Inc., Tokyo, Japan.
Takasaki
K
K
Mochizuki
A
A
Tamura
N
N
Higashide
Y
Y
Yamaura
T
T
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006633:Histamine Antagonists; D006801:Humans; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011817:Rabbits; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects*
D018927:Anti-Asthmatic Agents; C096516:F 1322; D006633:Histamine Antagonists; D016859:Lipoxygenase Inhibitors; D009281:Naphthalenes; D013930:Thromboxane-A Synthase