LG 30435, a new bronchodilator/antiallergic agent, inhibits PAF-acether induced platelet aggregation and bronchoconstriction.
LG 30435 is a quaternary phenothiazinic antihistamine, endowed with bronchodilator and antiallergic activity. Since PAF-acether (PAF) is a potential mediator of asthma, LG 30435 was assayed for its ability to counteract PAF-induced platelet aggregation (PA) in rabbit platelet rich plasma and bronchoconstriction (BC) in anaesthetized guinea-pigs, in comparison with other antihistamines. LG 30435 was the most potent and selective inhibitor of PAF-induced PA (IC50: 66 microM), concentrations three and more than fifteen fold higher being needed to inhibit PA induced by collagen and arachidonic acid respectively. The other antihistamines, namely mepyramine, promethazine, mequitazine, thiazinamium methyl sulfate and ketotifen were less potent inhibitors of PAF-induced PA, while interfered at lower concentrations with collagen-induced PA. LG 30435 and thiazinamium, administered intravenously, inhibited dose-dependently PAF-induced BC, starting from the dose of 0.1 mumol/kg. The ED50 of LG 30435 was 0.28 mumol/kg, while the inhibition obtained with thiazinamium did not reach 50% even at 3 mumol/kg. Ketotifen and promethazine were partially active only at 3 mumol/kg, while mequitazine and mepyramine were inactive up to this dose. These results show that LG 30435 is endowed with a peculiar anti-PAF action, which may be advantageous in the treatment of asthma.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D003094:Collagen / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits
D001095:Arachidonic Acids; D001993:Bronchodilator Agents; D010640:Phenothiazines; D010972:Platelet Activating Factor; C049967:LG 30435; D016718:Arachidonic Acid; D003094:Collagen