The antiplatelet effect of alprazolam, an antidepressive anxiolytics and platelet activating factor (PAF) antagonist, was studied in the platelet obtained from male rabbits. The IC50 of alprazolam (AA0 in the platelet aggregation and secretion
induced by thrombin, 0.25 unit/ml (TB) were 2.63×10E-4 M and 2.51×10E-4 M, respectively. The AA-induced increase of platelet cAMP level was not affected by TB, but the AA-induced cGMP increase was enhanced by TB, AA did not affect the platelet IP3 level and TB induced the significant increase of that level. However, the TB-induced increase of platelet IP3 was significantly enhanced by AA pretreatment. But the TB-induced increase of platelet [CA2+] was significantly suppressed by AA in the dose dependent manner. [3H] thymidine-DNA synthesis of bovine pulmonary artery endothelium (BPAE) and BC3Hl cells were dose-dependently inhibited by AA. These results suggested that the antiplatelet effect of alprazolam may be ascribed to its activity on the cyclic nucleotide metabolism, but the alprazolam-induced enhancement of the platelet IP3 increase in response to thrombin should be further studied, and that the antimitotic activities of alprazolam on the vascular endothelial cessl would be beneficial to the control of atherogenesis.
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