[Anti-allergic effects of (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046), a specific thromboxane (TX) A2 synthetase inhibitor: effect of OKY-046 on II-IV type allergic reactions].
We studied the effects of OKY-046 on types II, III and IV allergic reactions, as classified by Coombs and Gell. In Type II, OKY-046 at 30-100 mg/kg intraduodenally (i.d.) and at 1-30 mg/kg intravenously (i.v.) inhibited the bronchoconstriction in a dose-dependent manner after Forssman antigen injection. Aspirin (3 mg/kg, i.v.) also suppressed it. OKY-046 (30-100 mg/kg, i.d.) suppressed the increase of TXB2 level in the plasma in a dose-dependent manner. However, there was no effect of OKY-046 and aspirin on the decrease in complement activity (CH50), platelets and leukocytes. Additionally, OKY-046 (300 mg/kg, p.o.) prolonged the survival time following Forssman antigen injection. However, the immune hemolysis reaction was not prevented by OKY-046 (10(-6)-10(-3) M). FUT-175 protected against the Forssman shock at 1 mg/kg, i.v. and the in vitro immune hemolysis reaction at 10(-5) M. In Type III, OKY-046 (300 mg/kg, p.o.) significantly suppressed the direct passive Arthus reaction and immune complex nephritis in rats. There was no effect of OKY-046 on the delayed-type hypersensitive response to picryl chloride in mice. We think that OKY-046 should be a beneficial drug for the treatment of types II and III allergic reactions.
Kikuchi
S
S
Research Laboratories, Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan.
Takehana
Y
Y
Hamano
S
S
Ichikawa
K
K
Komatsu
H
H
Okegawa
T
T
Ikeda
S
S
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D001183:Arthus Reaction / Q000188:drug therapy; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005577:Forssman Antigen / Q000276:immunology*; D006168:Guinea Pigs; 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; D009393:Nephritis / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D015478:Antigens, Heterophile; D008689:Methacrylates; D013929:Thromboxane B2; D005577:Forssman Antigen; D013930:Thromboxane-A Synthase; C034364:ozagrel