Five potential /3-adrenoceptor blocking (BAB) compounds, alkylesters of 4-[(2-hydroxy-3-alkylamino)propoxy] phenylcarbamic acid, and eight calcium channel blockers (CB), i.e. nifedipine, nimodipine, niludipine, nitrendipine, verapamil, gallopamil, mepamil and diltiazem, were compared as to their inhibitory effect on thrombin induced aggregation of washed rat platelets and their effect on dynamies/disorder of liposomal membranes prepared from platelet lipids, studied by EPR spectroscopy of a lipid spin probe. The anti-aggregatory potency of the BAB and CB drugs was effective within the concentration range of 0.01-1 mmol/1. The antiaggregatory potency of BAB increased in the order BL- 143< BL-243< BL-343 < BL-443 < BL-543 and among the CB, nifedipine and diltiazem were the least potent, whereas nitrendipine and mepamil were the most potent drugs. The potency of the other CB tested was intermediate. The BAB drugs increased the dynamies/disorder of the liposomes in the same order as they inhibited platelet aggregation, whereas there was no relationship between antiaggregatory effect of CB and their influence on dynamies/disorder of the liposomes. Nifedipine, nimodipine, niludipine and nitrendipine had a minor perturbation effect on the liposomes, whereas verapamil, mepamil, gallopamil and diltiazem pronouncedly increased the dynamies/disorder of the hydro- phobic part of the liposomes. The results indicate that the anti-aggregatory activity of BAB drugs may be mediated, at least partially, through their perturbation effect on the lipid part of biological membranes.
To predict more precisely the effect of stobadine, a pyridoindole antioxidant agent, in the whole organism, we studied its effect on opsonized zymosan-stimulated free radical generation in whole blood, on superoxide generation in the mixture of PMNL : platelets (1:50), as well as on superoxide generation and myeloperoxidase release in isolated PMNL. Without stimulation, stobadine had no effect on reactive oxygen species (ROS) generation and myeloperoxidase release. Stobadine in a concentration of 10 or 100 µmol/l significantly decreased luminol-enhanced chemiluminescence in opsonized zymosan-stimulated whole blood. In concentrations of 10 and 100 µmol/l, it reduced myeloperoxidase release from isolated neutrophils. Stobadine significantly decreased superoxide generation in isolated neutrophils in 100 µmol/l concentration. Its effect was much less pronounced in the mixture of neutrophils and platelets in the ratio close to physiological conditions (1:50). Our results suggest that stobadine might exert a beneficial effect in diseases or states where superfluous ROS generation could be deleterious.