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. 1992 May;106(1):55–60. doi: 10.1111/j.1476-5381.1992.tb14292.x

Studies on curare-like action of 2,2',2''-tripyridine in the mouse phrenic nerve-diaphragm.

S Y Lin-Shiau 1, K S Hsu 1, W M Fu 1
PMCID: PMC1907464  PMID: 1504731

Abstract

1. 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 microM, which had no significant effect on the twitch amplitudes evoked by direct muscle stimulation. 2. 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. 3. Pretreatment with either 0.7 microM (+)-tubocurarine or 2.2 microM succinylcholine shifted the concentration-inhibition curve of 2,2',2''-tripyridine to the left. 4. 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 alpha-bungarotoxin and also specifically inhibited the binding of [125I]-alpha-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. 5. 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.). 6. 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.

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Selected References

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