Treatment of tabun poisoned guinea-pigs with atropine, HLö 7 or HI 6: effect on respiratory and circulatory function.
The oxime HI 6 (in combination with atropine) is considered to be an effective antidote in soman intoxication but was shown to be less effective in tabun poisoning. In contrast to HI 6, first in vitro studies with HLö 7 demonstrated a reasonable reactivating potency at acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the therapeutic efficacy of HLö 7, HI 6 and obidoxime (with and without atropine) was compared in tabun poisoned guinea-pigs. In addition, the therapeutic effect of atropine in guinea-pigs poisoned by various doses of tabun was investigated. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the carotid artery, jugular vein and trachea were cannulated. After baseline measurements the animals received tabun, 60, 180 or 300 micrograms/kg, and 2 min later the antidotes (all i.v.): obidoxine, HLö 7, or HI 6 (30 or 100 mumol/kg, each) or atropine 10 mg/kg or a combination of atropine and one of the oximes. Respiratory and circulatory parameters were recorded for 60 min or until the death of the animal. Erythrocyte, brain and diaphragm AChE activity was determined in every animal after the experiment. Poisoning by tabun resulted in a rapid deterioration of respiratory function and respiratory arrest within 5 min. Atropine treatment was very effective in improving the respiratory function after tabun 60 micrograms/kg but was ineffective after tabun 300 micrograms/kg. However, circulatory parameters were restored almost completely in all atropine therapy groups. Therapy of tabun 300 microns/kg poisoned animals with atropine plus oxime (30 micromol/kg) improved respiration to a variable extent and restored circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Worek
F
F
Institut für Pharmakologie und Toxikologie, Akademie des Sanitäts- und Gesundheitswesens der Bundeswehr, Garching, Germany.
Kirchner
T
T
Szinicz
L
L
D000818:Animals; D001285:Atropine / Q000627:therapeutic use*; D001775:Blood Circulation / Q000187:drug effects*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D007928:Lethal Dose 50; D009768:Obidoxime Chloride / Q000627:therapeutic use; D062025:Organophosphate Poisoning; D010755:Organophosphates / Q000037:antagonists & inhibitors*; D010091:Oximes; D011725:Pyridines / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000627:therapeutic use; D012119:Respiration / Q000187:drug effects*
D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D009768:Obidoxime Chloride; D001285:Atropine; C022870:asoxime chloride; C009374:tabun