RT Journal Article SR Electronic T1 In vivo rat hemoglobin thiyl free radical formation following administration of phenylhydrazine and hydrazine-based drugs. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 799 OP 803 VO 16 IS 6 A1 K R Maples A1 S J Jordan A1 R P Mason YR 1988 UL http://dmd.aspetjournals.org/content/16/6/799.abstract AB We have employed the ESR spin trapping technique in vivo to detect the formation of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)/hemoglobin thiyl free radical adduct in the blood of rats following administration of hydrazine-based drugs. The drugs examined were isoniazid, iproniazid, phenelzine, and hydralazine. In addition, phenylhydrazine and acetylhydrazine were also studied in a like manner. Of the four drugs, only phenelzine and iproniazid were able to induce the formation of the DMPO/hemoglobin thiyl free radical adduct in vivo, whereas only phenelzine and hydralazine were able to form this adduct in vitro. We were able to decrease the in vivo iproniazid-induced adduct formation by pretreating the rats with bis-para-nitrophenylphosphate, an arylamidase inhibitor. Our results support the idea that iproniazid is hydrolyzed in the liver to a more reactive metabolite, most likely isopropylhydrazine, which is subsequently released into the blood stream. In addition to the drug studies, experiments were performed to provide additional evidence that the radical adduct we detected was indeed of a hemoglobin thiyl free radical. Studies employing alpha-phenyl-N-t-butylnitrone (PBN) as the spin trap in place of DMPO also showed the formation of the PBN/hemoglobin thiyl free radical adduct.