Efficacy of HI-6 and HLö-7 in preventing incapacitation following nerve agent poisoning.
The therapeutic efficacy of the oximes HI-6 and HLö-7 (132.5 mumol/kg), in combination with atropine, in soman- or tabun-intoxicated guinea pigs was compared, particularly with respect to recovery of shuttlebox performance and electroencephalograms (EEGs). After 1.5 x LD50 soman SC, therapy with HI-6 or HLö-7 resulted in survival of 87.5% of the animals in each group. In both groups postintoxication performance decrements and EEG abnormalities lasted approximately 2 weeks after intoxication. After 3 x LD50 soman all HLö-7-treated animals died within 5 h; 70% of the HI-6-treated animals were still alive after 8 h; however, only 10% survived more than 24 h. After 2 x LD50 tabun 36% of the HI-6-treated animals died; HLö-7 prevented lethality and led to faster recovery of performance and EEG than after HI-6. Even after 7.5 x LD50 tabun, followed by HLö-7, full recovery was reached within 1 week in the surviving animals (82%). In soman-intoxicated guinea pigs HI-6 is therapeutically slightly more effective than HLö-7. HLö-7 is far more effective, under similar conditions, against tabun intoxication than HI-6.
Melchers
B P
BP
Department of Experimental Pharmacology, TNO-Pharma, HV Rijswijk, The Netherlands.
Philippens
I H
IH
Wolthuis
O L
OL
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D006168:Guinea Pigs; D007928:Lethal Dose 50; D010755:Organophosphates / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010091:Oximes; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D015656:Respiratory Mechanics / Q000187:drug effects; D012999:Soman / Q000037:antagonists & inhibitors* / Q000633:toxicity
D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; C009374:tabun