Accession Number : ADA317930

Title :   Characterization of the Anticyanide Effect of Methemoglobinemia Induced by Candidate Pretreatment Drugs in an Anesthetized Animal Model.

Descriptive Note : Final rept.,

Corporate Author : BATTELLE MEMORIAL INST COLUMBUS OH

Personal Author(s) : Olson, Carl T. ; Reid, Frances M. ; Menton, Ronald G. ; Audet, Kandy K. ; Hayes, Timothy L.

PDF Url : ADA317930

Report Date : SEP 1996

Pagination or Media Count : 276

Abstract : 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 mg/kg 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.

Descriptors :   *SODIUM, *CYANIDES, *MEDICAL SERVICES, *ANESTHESIA, *METHEMOGLOBIN, MODELS, MEDICINE, AMINES, TOLERANCE, DOSAGE, POISONING, ANIMALS, DRUGS, INTERVENTION, HYDROXYL RADICALS, BLOOD DISEASES, DOGS.

Subject Categories : Biochemistry
      Medicine and Medical Research
      Inorganic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE