Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity reactions: (II). Antagonistic effect of epinastine on chemical mediators, mainly antihistaminic and anti-PAF effects.
Anti-histamine and anti-PAF effects of epinastine were tested in rats, guinea pigs and rabbits. Epinastine showed a potent histamine H1-blocking effect, but the potency was slightly less than that of ketotifen in histamine-induced contraction of guinea pig ileum and histamine-induced cutaneous reactions in rats. In histamine-induced dye leakage into the nasal cavity tested in rats, the drug was slightly more potent than ketotifen and azelastine. Epinastine as well as ketotifen suppressed rabbit platelet aggregation induced by PAF at higher concentrations compared with WEB 2086, a specific PAF-antagonist. In the bronchospasm induced by PAF in guinea pigs, epinastine was more effective than ketotifen in inhibiting the bronchoconstriction, while it showed no remarkable effect on the hypotension induced by PAF. Epinastine caused a potent antagonistic effect on LTC4-induced contraction of isolated guinea pig trachea. In conclusion, the potent anti-histamine, anti-PAF and anti-LT effects of epinastine may significantly contribute to its antiallergic activity.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
C
C
Kamei
M
M
Mio
K
K
Kitazumi
S
S
Tsujimoto
T
T
Yoshida
Y
Y
Adachi
K
K
Tasaka
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D003984:Dibenzazepines / Q000494:pharmacology*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000494:pharmacology
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D013189:SRS-A; C053090:epinastine