[Anti-allergic effects of (E)-3-[p-(1H-imidazol-1-lylmethyl) phenyl]-2-propenoic acid (OKY-046), a specific thromboxane (TX) A2 synthetase inhibitor: effects on type I allergic reactions].
We studied the effects of OKY-046 on type I allergic reactions. OKY-046 (100 mg/kg) given orally suppressed antigen-induced bronchoconstriction and TXB2 generation in broncho alveolar lavage fluid in rats passively sensitized with anti-DNP-As monoclonal IgE. At the dose of 30 mg/kg given intraduodenally, it also inhibited antigen-induced bronchoconstriction in guinea pigs passively sensitized with anti DNP-As serum and actively sensitized with ovalbumin. However, aspirin (30 mg/kg) didn't suppressed them significantly. Azelastine (10 mg/kg) inhibited bronchoconstriction in passively sensitized rats and actively sensitized guinea pigs. In 48 hour homologous PCA reactions of rats and mice, oral administration of OKY-046 (300 mg/kg) and tranilast (100 mg/kg) suppressed the extravasated dye in the skin. OKY-046 decreased histamine release from passively sensitized rat peritoneal exudate cells. There was no effect of OKY-046 on SRS-A and leukotriene release from actively sensitized guinea pig lungs and passively sensitized rats. In conclusion, we think that OKY-046 should be an useful asthmatic drug or anti-allergic drug by oral administration.
Research Laboratories, Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan.
Y
Y
Takehana
S
S
Kikuchi
K
K
Hara
S
S
Hamano
H
H
Komatsu
A
A
Ujiie
T
T
Okegawa
S
S
Ikeda
D000179:Acrylates / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001980:Bronchi / Q000187:drug effects*; D003864:Depression, Chemical; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D008689:Methacrylates; D013189:SRS-A; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; C034364:ozagrel