Studies on curare‐like action of 2,2′,2″‐tripyridine in the mouse phrenic nerve‐diaphragm

S. Y. Lin‐Shiau, K. S. Hsu, W. M. Fu

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The curare‐like action of 2,2′,2″‐tripyridine (a synthetic by‐product of the herbicide, paraquat) was studied in mouse phrenic nerve‐diaphragm preparation. The inhibition by 2,2′,2″‐tripyridine of nerve‐evoked twitches was dependent on the concentration, ranging from 1 to 100 μm, which had no significant effect on the twitch amplitudes evoked by direct muscle stimulation. The twitch inhibition by 2,2′,2″‐tripyridine was reversible and could be antagonized by anticholinesterase agents such as neostigmine, physostigmine as well as ecothiophate. Pretreatment with either 0.7 μm (+)‐tubocurarine or 2.2 μm succinylcholine shifted the concentration‐inhibition curve of 2,2′,2″‐tripyridine to the left. 2,2′2″‐Tripyridine inhibited not only acetylcholine‐induced contracture of the denervated mouse diaphragm but also that of the chick biventer cervicis muscle. Like (+)‐tubocurarine, 2,2′,2″‐tripyridine protected the twitches from the inhibition by α‐bungarotoxin and also specifically inhibited the binding of [125I]‐α‐bungarotoxin to the mouse diaphragm. All of these findings indicate that 2,2′,2″‐tripyridine possesses curare‐like action and inhibits the muscle contractions through binding to postsynaptic acetylcholine receptors. The postsynaptic inhibition exhibited by 2,2′,2″‐tripyridine was also implicated in the tetanic fade, a decrease in the amplitude of miniature endplate potential (m.e.p.p.) and endplate potential (e.p.p.). The clinical implication of these findings is that 2,2′,2″‐tripyridine may be involved in the cause of respiratory failure in paraquat‐intoxicated workers since 2,2′,2″‐tripyridine is a by‐product of paraquat synthesis. 1992 British Pharmacological Society

Original languageEnglish
Pages (from-to)55-60
Number of pages6
JournalBritish Journal of Pharmacology
Volume106
Issue number1
DOIs
Publication statusPublished - 1992 May

All Science Journal Classification (ASJC) codes

  • Pharmacology

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