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The Effects of an Antimetastatic Agent, (±)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane (ICRF 159), on Platelet Behavior

Cancer Chemotherapy Department, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, WC2A 3PX [A. A., K. H.], and Glaxo Research Limited, Sefton Park, Stoke Poges, Buckinghamshire [D. B.], England

Some agents that inhibit platelet aggregation, e.g., aspirin and dipyridamole, have been reported to prevent metastasis formation. To see whether inhibition of platelet aggregation could account for the antimetastatic action of (±)-1,2-bis(3,5-dioxopiperazin-1-yl)propane, this compound was investigated in vivo for any effects on platelet behavior and thrombogenesis. (±)-1,2-Bis(3,5-dioxopiperazin-1-yl)propane inhibited the formation of platelet thrombi in blood vessels on the surface of the rat brain and in the hamster cheek pouch. 1,2-Bis(dioxo-4-methylpiperazin-1-yl)ethane, a closely related analog of (±)-1,2-bis(3,5-dioxopiperazin-1-yl)propane, but without antimetastatic action, inhibited thrombus formation in vivo as effectively as (±)-1,2-bis(3,5-dioxopiperazin-1-yl)propane. It seems unlikely therefore that the antimetastatic action of (±)-1,2-bis(3,5-dioxopiperazine-1-yl)propane derives from its effects on thrombogenesis. Neither platelet numbers nor the ionized plasma calcium concentrations were changed after (±)-1,2-bis(3,5-dioxopiperazin-1-yl)propane administration.

Received 6/10/74. Accepted 12/23/74.