Effect of the selective PAF antagonist SM‐10661 on an asthmatic model. 2. Effect on antigen‐induced dual asthmatic response and infiltration of leukocytes into airways in actively sensitized conscious guinea pigs

Abstract

The effect of a selective platelet-activating factor (PAF) receptor antagonist, SM-10661, on antigen-induced dual asthmatic response and leukocyte infiltration into the airways of actively sensitized conscious guinea pigs was investigated. The animals were pretreated with mepyramine maleate (10 mg/kg i.p.) and then challenged with ovalbumin. The inhalation of ovalbumin caused an immediate decline in specific airway conductance (sGaw) which peaked at 5 min after the challenge. sGaw gradually returned to the baseline 6 hr after the challenge. After the early asthmatic response (EAR), a second phase change, a late asthmatic response (LAR) in sGaw peaking at 17-20 hr was observed. When 1% w/v disodium cromoglycate was inhaled for 2 min on two occasions, EAR was not affected, but LAR was significantly inhibited. Oral administration of 50 mg/kg fenoterol (30 min before challenge) significantly inhibited EAR, but had no significant effect on LAR. SM-10661 administered orally 1 hr before the challenge inhibited EAR dose-dependently (50% inhibitory dose (ID50); 59 mg/kg, but was even more effective against the LAR (ID50); 13-16 mg/kg). When 30 mg/kg of SM-10661 was administered orally 6 hr after ovalbumin challenge, LAR was completely inhibited. The number of total cells, macrophages and eosinophils in bronchoalveolar lavage fluids rose significantly 17 hr after antigen challenge compared to that observed after saline challenge. The number of neutrophils and lymphocytes also increased in response to the ovalbumin challenge, but not significantly. SM-10661 (30 mg/kg) administered orally 1 hr before the challenge significantly inhibited the increase in total cells, macrophages and eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of leukotriene formation and IL-8 release by the PAF-receptor antagonist SM-12502

“…Thus, it was the purpose of this study to investigate the role of the new PAF receptor antagonist (+)-cis-3,5,-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride, SM-12502 (16)(17)(18)(19) on the autocrine and paracrine cell activation of peripheral leukocytes by the use of distinct cell stimuli, which either bypass membraneous signaltransduction (e.g. Ca ionophore A23187), or activate cellular responses via ligand-receptor coupling (fMLP), or which directly stimulate heterotrimeric G-proteins (sodium fluoride, NaF).…”

Sodium cromoglycate and doxantrazole are oxygen radical scavengers

“…Evidence from previous publications suggests that there are some other mechanisms of actions of SCG in addition to its known anti-allergic properties. 1) The early asthmatic reaction (EAR) was not affected after inhalation of SCG in an ovalbumin model of airway hyperresponsiveness in the guinea pig, but the late asthmatic reaction (LAR) was significantly inhibited [3]. 2) SCG reduced injury on the irradiated side of rat lung [4].…”