Depletion of Platelet Amine Storage Granules by the Antithrombotic Agent, Suloctidil

Summary

Suloctidil, a compound with antithrombotic properties in animal models, causes depletion of human platelet serotonin stores during 1–5 hr incubation with platelet-rich plasma in vitro. This effect is not attended by leakage of cytoplasmic nucleotides or by alterations in cyclic AMP metabolism, malondialdehyde production or energy balance. 5HT uptake was also inhibited but uptake of adenine was not. 5HT released by suloctidil appeared in the supernatant as oxidation products, though the amine also accumulated when re-uptake was blocked by imipramine.

• References

• 1 Cazenave J. P, Reimers H. J, Packham M. A, Mustard J. F. 1977; Effect of reserpine on rabbit platelet aggregation and adherence to collagen of injured rabbit aorta. Biochemical Pharmacology 26: 149.
• 2 Da Prada M, Bartholini G, Pletscher A. 1965; Effect of monoamine liberators on the metabolism of 5 hydroxytryptamine in blood platelets. Biochemical Pharmacology 14: 1721.
• 3 De Gaetano G, Miragliotta G, Roncucci R, Lanse J, Lambelin G. 1976; Suloctidil: A novel inhibitor of platelet aggregation in human beings. Thrombosis Research 8: 361.
• 4 De Gaetano G, Roncaglione M. C, Miragliotta G, Wielosz M, Garattini S. 1977; In vitro effects of suloctidil on ¹⁴C-5 hydroxytryptamine uptake and liberation in rat platelets. Pharmacological Research Communications 9: 315.
• 5 Gurewich V, Lipinski B. 1976; Evaluation of antithrombotic properties of suloctidil in comparison with aspirin and dipyridamole. Thrombosis Research 9: 101.
• 6 Haverbach B. J, Dutcher T. F, Shore P. A, Tomich E. G, Terry L. L, Brodie B. B. 1957; Serotonin changes in platelets and brain induced by small daily doses of reserpine: Lack of effect of depletion of platelet serotonin on hemostatic mechanisms. New England Journal of Medicine 256: 343.
• 7 Macfarlane D. E, Mills D. C. B. 1975; The effects of ATP on platelets: Evidence against the central role of released ADP in primary aggregation. Blood 46: 309.
• 8 Macfarlane D. E, Gardner S, Lipson C, Mills D. C. B. 1977; Malondialdehyde production by platelets during secondary aggregation. Thrombosis and Haemostasis 38: 1002.
• 9 Mills D. C. B, Roberts G. C. K. 1967; Effects of adrenaline on human blood platelets. Journal of Physiology 193: 443.
• 10 Mills D. C. B. 1974. The platelet as a point of attack for antithrombotic agents. In: Medicinal Chemistry IV. (ed.) Mass J. Amsterdam: Elsevier; 197.
• 11 Mills D. C. B, Macfarlane D. E. 1975; Cytochalacins: Effects on platelet aggregation, adenylate cyclase and membrane transport processes. Thrombosis et Diathesis Haemorrhagica 34: 917.
• 12 Mills D. C. B, Macfarlane D. E. 1976; Suloctidil: A potential antithrombotic agent. Effects on human platelets in vitro. Federation Proceedings 35: 807.
• 13 Mitchell J. R. A, Sharp A. A. 1964; Platelet clumping in vitro. British Journal of Haematology 10: 78.
• 14 Mustard J. F, Rowsell H. C, Smythe H. A, Senyi A, Murphy E. A. 1967; The effect of sulfinpyrazone on platelet economy and thrombus formation in rabbits. Blood 29: 859.
• 15 Nickerson M, Collier B. 1975. In: Pharmacological Basis of Therapeutics. (eds.) Goodman L. S, Gilman A. New York: Macmillan; 557.
• 16 O’Brien J. R. 1964; A comparison of platelet aggregation produced by seven compounds and a comparison of their inhibitors. Journal of Clinical Pathology 17: 275.
• 17 Pletscher A, Burkard W. P, Tranzer J. P, Gey K. P. 1967; Two sites of 5 hydroxytryptamine uptake in blood platelets. Life Sciences 6: 273.
• 18 Reimers H. J, Allen D. T, Feuerstein I. A, Mustard J. F. 1975; Transport and storage of serotonin by thrombin-treated platelets. Journal of Cell Biology 65: 359.
• 19 Roba J, Claeys M, Lambelin G. 1976; Antithrombogenic effects of suloctidil. European Journal of Pharmacology 37: 265.
• 20 Roba J, Reuse-Blom S, Lambelin G. 1976; In vivo antispasmodic activity of suloctidil. Archives Internationales de Pharmacodynamie 221: 54.