title: A comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit.
abstract: This study compared the efficacy of HI6 and 2-PAM against nerve agent (soman, tabun, sarin, and VX)-induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted of oxime (100 mumol/kg) + atropine (13 mg/kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 3-5 times more effective than 2-PAM. In contrast, HI6 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + HI6 alone. Both oximes were highly effective against sarin and VX. These findings suggest that HI6 could replace 2-PAM as therapy for nerve agent poisoning, because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals, it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.
authors.affiliation: Drug Assessment Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD.
authors.forename: I
authors.initials: I
authors.lastname: Koplovitz
authors.forename: J R
authors.initials: JR
authors.lastname: Stewart
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use; D001285:Atropine / Q000494:pharmacology; D002619:Chemical Warfare Agents / Q000506:poisoning*; D002800:Cholinesterase Inhibitors / Q000506:poisoning; D002801:Cholinesterase Reactivators / Q000494:pharmacology / Q000627:therapeutic use; D003975:Diazepam / Q000494:pharmacology; D007928:Lethal Dose 50; D008297:Male; D062025:Organophosphate Poisoning; D010755:Organophosphates / Q000037:antagonists & inhibitors; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors*; D009946:Organothiophosphorus Compounds / Q000037:antagonists & inhibitors / Q000506:poisoning; D010091:Oximes; D011041:Poisoning / Q000188:drug therapy; D011220:Pralidoxime Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D011817:Rabbits; D012524:Sarin / Q000037:antagonists & inhibitors / Q000506:poisoning; D012999:Soman / Q000037:antagonists & inhibitors / Q000506:poisoning; D013047:Specific Pathogen-Free Organisms
chemical_list: D000931:Antidotes; D001285:Atropine; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D003975:Diazepam; D010755:Organophosphates; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D011729:Pyridostigmine Bromide; D012524:Sarin; D012999:Soman; C009680:VX-agent; C022870:asoxime chloride; C028797:pralidoxime; C009374:tabun