Influence of propranolol, pindolol, practolol and talinolol on arachidonic acid (AA)- and U-46619-induced aggregation and on AA-induced thromboxane A2 formation in platelets.

The effects of four beta-adrenoceptor blocking agents on arachidonic acid (AA)-induced platelet aggregation and thromboxane (TX) formation in human and rabbit platelet-rich plasma (PRP) as well as their influence on prostaglandin endoperoxide analogue (U-46619)-induced aggregation in human PRP were studied. The potency against AA-induced aggregation decreased in the following sequence: pindolol greater than propranolol greater than talinolol greater than practolol (without effect). Pindolol (0.1-1.0 mmol/l) inhibited both AA-induced aggregation and TX formation. The cyclooxygenase activity in ram seminal vesicle microsomes was suppressed by both pindolol isomers. Propranolol was without effect on the cyclooxygenase. This supports the assumption that the inhibitory activity of pindolol on AA-induced platelet aggregation is mediated by its inhibiting effect on platelet cyclooxygenase as the first step of the TX formation. Propranolol (IC50:0.2 mmol/l), talinolol (IC50:0.7 mmol/l) and pindolol (IC50:1.3 mmol/l) inhibited the U-46619-induced aggregation, whereas practolol remained without effect. The spectrum of the reported data with propranolol, talinolol and practolol may be assumed to allow the correlation of the results to both the membrane stabilizing effects and to lipophilicity of the drugs.