Comparison of methemoglobin formers in protection against the toxic effects of cyanide.
1. Certain compounds that oxidize hemoglobin to methemoglobin (MHb) also protect against cyanide. 2. Evidence presented here suggests that other mechanisms may be involved. 3. Male Swiss ICR mice were pretreated intraperitoneally (i.p.) with various doses of primaquine phosphate (primaquine), WR6026 (6-methoxy-8-(6-diethylamino-hexylamino) lepidine dihydrochloride), WR238605 (8-[(4-amino-1-methylbutyl) amino]-2,6-dimethoxy-4-methyl-5-(3-trifluoromethylphenoxy) quinoline succinate), p-aminooctoyl-phenone (PAOP), or p-aminopropiophenone (PAPP). 4. The compounds were administered 15 or 60 min before an intramuscular (i.m.) challenge with a 2 x LD50 dose (5.0-5.6 mg/kg) of sodium cyanide (NaCN). 5. Twenty-four hr mortality was assessed and survivors were tested for motor incapacitation. 6. Primaquine, PAPP and PAOP increased survival compared to untreated controls, while the other MHb formers were not effective (P less than 0.05). 7. PAOP is believed to form sufficient MHb only after 3 to 4 hr after administration; however it was found to be effective when administered 15 min before NaCN challenge in this study. 8. This suggests that MHb formation may not be the only factor responsible for PAOP's anti-cyanide efficacy.
Scharf
B A
BA
Division of Drug Assessment, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Fricke
R F
RF
Baskin
S I
SI
D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000378:metabolism; D007659:Ketones / Q000494:pharmacology*; D007928:Lethal Dose 50; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction; D011319:Primaquine / Q000494:pharmacology*; D011427:Propiophenones / Q000494:pharmacology*; D012966:Sodium Cyanide / Q000633:toxicity*
D000634:Aminoquinolines; D000814:Aniline Compounds; D006454:Hemoglobins; D007659:Ketones; D011427:Propiophenones; C055852:tafenoquine; C074798:4-aminooctoylphenone; C029564:4-aminopropiophenone; D008706:Methemoglobin; D011319:Primaquine; D012966:Sodium Cyanide; C080436:8-aminoquinoline