Comparison of the potency of five potential beta-adrenoceptor blocking drugs and eight calcium channel blockers to inhibit platelet aggregation and to perturb liposomal membranes prepared from platelet lipids.
Five potential beta-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 dynamics/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/l. 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 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 dynamics/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 dynamics/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 dynamics/disorder of the hydrophobic 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.
Ondriasová
E
E
Faculty of Pharmacy, Comenius University, Bratislava.
Ondrias
K
K
Stasko
A
A
Nosál
R
R
Csöllei
J
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000737:chemistry; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D008081:Liposomes; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D008081:Liposomes; D002118:Calcium