Ketotifen, an anti-asthmatic drugs protects platelet-activating factor-induced sudden death in rabbits

ABSTRACT

The effects of antiasthmatic drug; ketotifen on human platelet aggregation induced by platelet-activating factor [PAF], ADP, collagen and arachidonic acid [AA] have been investigated. Ketotifen selectively inhibited [at 0.04-4uM concentration] PAF-induced aggregation. Whereas other anti-asthma drugs such as sodium cromoglycate, theophylline and salbutamol had no effect. Similarly, ketotifen also inhibited the lethal effects of PAF in the rabbit. PAF [8-11ug/Kg i.v.] caused sudden death in rabbits due to platelet aggregation. Pretreatment of rabbits with ketotifen [1 mg/kg i.p.] protected conscious rabbits from PAF [11 ug/kg i.v.] -induced death. Since PAF is a powerful inducer of platelet aggregation via a mechanism mediated by specific PAF membrane receptors, our data is suggestive that ketotifen acts as a PAF antagonist in platelet aggregation