beta-Eudesmol as an antidote for intoxication from organophosphorus anticholinesterase agents.
beta-Eudesmol, a sesquiterpenol present in Chinese herbs, improved the tetanic contraction impaired by diisopropylfluorophosphate in isolated mouse diaphragm preparations by an inhibition of the regenerative acetylcholine release. The antagonism was enhanced when a small concentration of obidoxime was present. Neither enzyme reactivation nor curare-like action was evident. beta-Eudesmol (300 mg/kg, i.p.) elevated the LD50 of diisopropylfluorophosphate (s.c.) in control mice from 4.2 to 6.4 mg/kg and in mice pretreated with atropine from 7.8 to 10.6 mg/kg. In mice pretreated with atropine and obidoxime, beta-eudesmol showed a greater synergistic effect, increasing the LD50 from 281 to more than 800 mg/kg. beta-Eudesmol also markedly alleviated diisopropylfluorophosphate-induced muscle fasciculation, tremor and convulsion and prolonged the time to death. It is proposed that beta-eudesmol may be added to the standard antidotal regimen (atropine plus obidoxime) for treating organophosphate intoxication.
Chiou
L C
LC
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Ling
J Y
JY
Chang
C C
CC
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000931:Antidotes / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000037:antagonists & inhibitors / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009045:Motor Endplate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009388:Neostigmine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D000931:Antidotes; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D045787:Sesquiterpenes, Eudesmane; D013729:Terpenes; D007531:Isoflurophate; D009388:Neostigmine; C051082:beta-eudesmol; D001285:Atropine