[Inhibitory effects of AA-2414, a thromboxane (Tx) A2 receptor antagonist, on U-46619-, prostaglandin (PG) D2- and 9 alpha, 11 beta PGF2-induced contractions of guinea pig tracheas and isolated human bronchi].
The effects of a novel TXA2 receptor antagonist, AA-2414 [(+-)-7-(3,5,6-trimethyl-1,4-benzoquinone-2-yl)-7-phenyl-heptanoic acid], on U-46619-, PGD2- and 9 alpha, 11 beta-PGF2 alpha-induced contractions of isolated guinea pig tracheas and human bronchi were investigated. AA-2414 competitively inhibited the contractile responses of both human and guinea pig preparations induced by U-46619 with similar pA2 values (7.7 and 7.6, respectively). In addition, the compound also inhibited the contractions of both preparations caused by PGD2 and 9 alpha, 11 beta-PGF2 alpha, the IC50 values of which were 1.2 x 10(-7) and 1.8 x 10(-7) M in guinea pig tracheas and 2.8 x 10(-8) and 8.5 x 10(-8) M in human bronchi. These results suggest that AA-2414 may be a therapeutically useful drug for bronchial asthma.
Itoh
Y
Y
Department of Pneumology, Ohgaki Municipal Hospital.
Shindoh
J
J
Horiba
M
M
Kohno
S
S
Ohata
K
K
Ashida
Y
Y
Takagi
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016227:Benzoquinones; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D015237:Dinoprost / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006538:Heptanoic Acids; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015230:Prostaglandin D2 / Q000037:antagonists & inhibitors*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D016227:Benzoquinones; D006538:Heptanoic Acids; D011450:Prostaglandin Endoperoxides, Synthetic; D011809:Quinones; D017482:Receptors, Thromboxane; C060230:seratrodast; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D015230:Prostaglandin D2