Azelastine, a new antiallergic/antiasthmatic agent, inhibits PAF-acether-induced platelet aggregation, paw edema and bronchoconstriction.
Azelastine is a phthalazinone derivative with a wide spectrum of pharmacologically relevant activities. Since PAF-acether has been considered to be a potent mediator of asthma, azelastine was assayed for its ability to counteract PAF-acether-induced platelet aggregation, paw edema development and bronchoconstriction. Azelastine exerted a concentration-dependent inhibition of PAF-acether-induced platelet aggregation in human platelet rich plasma with an IC50 of 87 mumol/l and was as effective as ketotifen. PAF-acether-induced paw edema was reduced by intraperitoneal administration of azelastine resulting in an ID50 of 14.4 mg/kg after 2 h. By contrast, ketotifen was not able to inhibit edema development up to a dose of 32 mg/kg i.p. Azelastine and ketotifen, administered intravenously, dose-dependently inhibited PAF-acether-induced bronchoconstriction, starting from the dose of 0.01 mg/kg and resulting in ID50s of 0.03 and 0.02 mg/kg, respectively. These results show that azelastine is endowed with a peculiar anti-PAF-acether action, which may be advantageous in its therapeutic use, in the treatment of asthma.
Achterrath-Tuckermann
U
U
Department of Pharmacology, Asta Pharma AG, Frankfurt a.M., FRG.
Weischer
C H
CH
Szelenyi
I
I
D000818:Animals; D001986:Bronchial Spasm / Q000139:chemically induced / Q000517:prevention & control*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D010793:Phthalazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010793:Phthalazines; D010972:Platelet Activating Factor; D011724:Pyridazines; C020976:azelastine