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Abstract

The LD50 values of propylene glycol 1,2-dinitrate (PGDN) were determined in the rat, mouse, and cat. Injection of an LD50 in the rat causes almost complete conversion of the hemoglobin to methemoglobin, indicating that methemoglobinemia is the principal cause of death following PGDN administration.The metabolism of PGDN in vitro and in vivo gives rise to inorganic nitrite and inorganic nitrate, and the 1- and 2-isomers of propylene glycol mononitrate. The 2-isomer predominates, and it is suggested that there is a reaction favoring its formation. In vivo the mononitrates are themselves metabolized with the result that only small amounts are excreted. The major urinary metabolite is inorganic nitrate, accounting for 56% of the original injection of PGDN.PGDN is a potent vasodilator. An injection in the rat gives rise to a fall in blood pressure lasting several hours that may be due to the combined influence of the intact molecule of PGDN and its metabolites.It is concluded that there is little to distinguish the metabolism and pharmacology of PGDN from that of ethylene glycol dinitrate.