Characterization of the Anticyanide Effect of Methemoglobinemia Induced by Candidate Pretreatment Drugs in an Anesthetized Animal Model.
BATTELLE MEMORIAL INST COLUMBUS OH
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Task 92-28 was conducted to determine the protective efficacy provided by low methemoglobin MHb levels against a continuous sodium cyanide NaCN infusion, and to compare and quantitate the efficacy of long-acting and short-acting MHb-forming compounds in anesthetized canines. The time to respiratory arrest TRA was measured, after which the animals were revived with 10 mgkg of hydroxylamine iv. The average estimated protective percent MHb was 5.4 percent with a 95 percent upper tolerance bound of 6.4 percent. Three compounds that induce the formation of MHb, p-aminopropiophenone PAPP, p-aminoheptanophenone PAHP, and an 8-aminoquinoline WR242511, were effective in mitigating the effects of NaCN poisoning when compared to the controls. No statistically significant differences in efficacy were observed among the three compounds. Doses of two times the average concentration required to induce respiratory arrest 2xAvTRA were tested in animals pretreated with PAPP. All of the PAPP pretreated anesthetized animals achieved approximately 6.5 percent MHb, did not cease breathing, and did not require any other medical intervention to recover from the NaCN challenge.
- Medicine and Medical Research
- Inorganic Chemistry