Atropine and oxime treatment in lethal soman poisoning of anaesthetized guinea-pigs: HLö 7 dimethanesulfonate versus HI 6 dichloride.
The oxime HI 6 is considered to be effective in soman poisoning and less effective in tabun poisoning. Recently, HLö 7 was shown to reactivate acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the efficacy of HLö 7 and HI 6 was compared in soman poisoned guinea-pigs. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the a. carotis, v. jugularis and trachea were cannulated. After base line measurements soman 0.08 mg/kg (= 5 x LD50) or 0.16 mg/kg (= 10 x LD50) was injected intravenously, 2 min. later the antidotes were applied intravenously: HLö 7 0.03 or 0.1 mmol/kg, HI 6 0.03 or 0.1 mmol/kg, atropine 10 mg/kg, or a combination of atropine and an oxime. Respiratory and circulatory parameters were recorded for 60 min. or until the death of the animal. The injection of 5 x LD50 soman resulted in a rapid respiratory arrest followed by circulatory failure in the soman and soman plus oxime groups (survival time about 7 min). Atropine restored the circulatory parameters to base line but was unable to provide a sufficient respiratory function (survival time 26 min.). The combination therapy with atropine plus HLö 7 or HI 6 improved the respiration sufficiently, restored the circulation completely, and prolonged the survival time to about 50 min. Atropine treatment was insufficient in animals poisoned with 10 x LD50 soman. The combination of atropine and HLö 7 or HI 6 improved respiration, circulation, and survival time to various extent. Despite of the striking therapeutic effect no reactivation of erythrocyte AChE by the antidotes was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Worek
F
F
Institute of Pharmacology and Toxicology, Federal Armed Forces Medical Academy, BSW, Garching, Germany.
Szinicz
L
L
D000110:Acetylcholinesterase / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D010091:Oximes; D011041:Poisoning / Q000188:drug therapy; D011725:Pyridines / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D012119:Respiration / Q000187:drug effects; D012999:Soman / Q000506:poisoning*
D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D001285:Atropine; D012999:Soman; D000110:Acetylcholinesterase; C022870:asoxime chloride