[Pharmacological studies on KW-4679, an antiallergic drug. (1): Inhibitory effect on passive cutaneous anaphylaxis (PCA) and experimental asthma in rats and guinea pigs].
The present experiment was carried out to elucidate the antiallergic properties of KW-4679. Oral administration of KW-4679 showed a dose-dependent inhibition on the IgE-mediated 48-hr homologous PCA in rats, with an ID50 value of 0.04 mg/kg. Passive anaphylactic broncho-constriction in guinea pigs mediated by IgE-like homologous antibody against ovalbumin was prevented dose-dependently by treatment with KW-4679 at doses of 0.03-1 mg/kg, p.o. KW-4679 also inhibited the IgE-mediated active anaphylactic bronchoconstriction in rats. In passively sensitized guinea pigs, the inhalation of aerosol antigen decreased the dynamic compliance of the lung and increased the mean pulmonary resistance. Pretreatment with KW-4679 (0.03-1 mg/kg, p.o.) inhibited antigen-induced airway obstructions. Oral administration of KW-4679 significantly protected rats from compound 48/80-induced lethality. These results indicate that KW-4679 might be useful in the treatment of allergic diseases such as asthma.
Ishii
H
H
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Sasaki
Y
Y
Ikemura
T
T
Kitamura
S
S
Ohmori
K
K
D000284:Administration, Oral; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D016084:Bronchoconstriction / Q000187:drug effects; D003864:Depression, Chemical; D003990:Dibenzoxepins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008297:Male; D000069605:Olopatadine Hydrochloride; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D018926:Anti-Allergic Agents; D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride