LG 30435, a new bronchodilator/antiallergic agent, inhibits PAF-acether induced platelet aggregation and bronchoconstriction. 1986

M Criscuoli, and A Subissi, and L Daffonchio, and C Omini

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.

UI MeSH Term Description Entries
D008297 Male Males
D010640 Phenothiazines Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D001993 Bronchodilator Agents Agents that cause an increase in the expansion of a bronchus or bronchial tubes. Bronchial-Dilating Agents,Bronchodilator,Bronchodilator Agent,Broncholytic Agent,Bronchodilator Effect,Bronchodilator Effects,Bronchodilators,Broncholytic Agents,Broncholytic Effect,Broncholytic Effects,Agent, Bronchodilator,Agent, Broncholytic,Agents, Bronchial-Dilating,Agents, Bronchodilator,Agents, Broncholytic,Bronchial Dilating Agents,Effect, Bronchodilator,Effect, Broncholytic,Effects, Bronchodilator,Effects, Broncholytic
D003094 Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH). Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001095 Arachidonic Acids Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic

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