beta-Eudesmol as an antidote for intoxication from organophosphorus anticholinesterase agents.

Abstract

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.

• Authors: L C Chiou, J Y Ling, C C Chang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 292 Issue 2 Pg. 151-6 (Jan 13 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7720787 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Ulcer Agents
• Antidotes
• Cholinesterase Inhibitors
• Organophosphorus Compounds
• Sesquiterpenes, Eudesmane
• Terpenes
• Isoflurophate
• Neostigmine
• beta-eudesmol
• Atropine

Topics

• Animals
• Anti-Ulcer Agents (pharmacology)
• Antidotes (pharmacology)
• Atropine (pharmacology)
• Cholinesterase Inhibitors (toxicity)
• Electrophysiology
• Female
• In Vitro Techniques
• Isoflurophate (antagonists & inhibitors, toxicity)
• Lethal Dose 50
• Male
• Membrane Potentials (drug effects)
• Mice
• Mice, Inbred ICR
• Motor Endplate (drug effects)
• Muscle Contraction (drug effects)
• Muscle, Skeletal (drug effects, innervation)
• Neostigmine (pharmacology)
• Organophosphorus Compounds (antagonists & inhibitors, toxicity)
• Sesquiterpenes, Eudesmane
• Terpenes (pharmacology)