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Influence of Serotonin Antagonists on Nitrogen Mustard Intoxication¹

( Western Institute for Cancer and Leukemia Research, Los Angeles, California)

The administration of a pyrazolone compound before and after a single I.P. LD_90–100 does of nitrogen mustard produced a marked reduction of the expected mortality in mice. The pyrazolone was most effective I.P. but it was also effective P.O. This protection was also observed in mice receiving the nitrogen mustard I.V. When the pyrazolone was given in multiple daily doses a greater degree of protection was obtained than with a single dose. The protective effect of the pyrazolone was observed at different toxic levels of nitrogen mustard. The leukopenia induced by the nitrogen mustard was less in extent and duration in pyrazolone-treated mice.

A number of agents with antiserotonin activity were tested; several of these compounds were found to have some ability to reduce the toxicity of nitrogen mustard.

¹ Communication No. 11. This study was supported by grants from the following foundations: The Milheim Foundation for Cancer Research, R. C. Baker, Conrad N. Hilton, Joseph Lowitz, Lidow, William Morris Agency, and Robert H. and Clare M. Avnet. Also the Horace E. Altfeld, Susan Gorshow, Abe Yaras, Leo Cholodenko, and Harold Rappaport Memorial Funds, North American Aviation Employees Donate Once Club, and the International Rectifier Corporation.

Received 5/25/64. Revised 11/13/64.