Pyrazolidine derivatives: a comparative study of their effects on platelet aggregation

Quantitative studies were carried out of the in vitro and ex vivo effects of phenylbutazone and 3-oxoalkyl substituted diphenyldioxopyrazolidines (kebuzone, tribuzone, benzopyrazone) on platelet aggregation. The specified pyrazolidine derivatives exhibited in vitro inhibitory effects on secondary platelet aggregation (induced by adrenaline and collagen), commensurable with the effects of sulfinpyrazone. The ex vivo efficacy was markedly influenced by the height of the drug level in blood and by differences in the elimination kinetics of the pyrazolidine derivatives in human organism. Inhibitory activities against primary aggregation (induced by ADP and thrombin) were found in vitro mainly in the phenyloxoalkyl derivative of diphenyldioxopyrazolidine (benzopyrazone) and its analogues. By substitution on the phenyl attached to its alkyl side chain (for example, by a halogen in the meta position), compounds were obtained which also possessed higher activities inhibiting secondary platelet aggregation.