In Vitro Oxime-induced Reactivation of Various Molecular Forms of Soman-inhibited Acetylcholinesterase in Striated Muscle from Rat, Monkey and Human

Overview

Journal Arch Toxicol

Specialty Toxicology

Date 1994 Jan 1

PMID 7857205

Citations 2

Authors

J G Clement

N Erhardt

Affiliations

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Abstract

The purpose of this study was to compare the in vitro reactivation of the various molecular forms of soman-inhibited acetylcholinesterase by oximes such as HI-6, toxogonin and PAM, in striated muscle tissue from three species-rat, monkey and human. To simulate the various in vivo conditions the oxime was present either 5 min before and after (Pre-Post) or 5 min after (Post) exposure to the nerve agent soman. In the Pre-Post mode the oxime effects would result from a combination of not only shielding of acetylcholinesterase from soman inhibition but also from immediate reactivation of soman-inhibited acetylcholinesterase. In the Post experimental group the increase in soman-inhibited acetylcholinesterase activity was due to reactivation. HI-6 (Pre-Post) increased significantly the activity of soman-inhibited acetylcholinesterase in the rat, human and monkey muscle. HI-6 (Post) was a highly effective reactivator of soman-inhibited acetylcholinesterase in the rat muscle and moderately so in the human and monkey muscle. Toxogonin (Pre-Post) and toxogonin (Post) were effective in increasing soman-inhibited acetylcholinesterase activity in rat muscle but were relatively ineffective in the human and monkey muscle. PAM (Pre-Post) and PAM (Post) were ineffective in increasing soman-inhibited acetylcholinesterase activity in muscle from all species examined. Effectiveness of oxime-induced reactivation of soman-inhibited acetylcholinesterase could be estimated from the total acetylcholinesterase activity which appears to reflect the results found with the individual molecular forms of acetylcholinesterase. In addition, SAD-128, a non-oxime bispyridinium compound, appeared to enhance significantly the HI-6 induced reactivation of soman-inhibited acetylcholinesterase in human but not rat striated muscle.

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References

Inestrosa N, Perelman A . Distribution and anchoring of molecular forms of acetylcholinesterase. Trends Pharmacol Sci. 1989; 10(8):325-9. DOI: 10.1016/0165-6147(89)90067-9. View

Clement J . Toxicology and pharmacology of bispyridium oximes--insight into the mechanism of action vs Soman poisoning in vivo. Fundam Appl Toxicol. 1981; 1(2):193-202. DOI: 10.1016/s0272-0590(81)80058-9. View

Harris L, Heyl W, Stitcher D, Broomfield C . Effects of 1,1'-oxydimethylene bis-(4-tert-butylpyridinium chloride) (SAD-128) and decamethonium on reactivation of soman- and sarin-inhibited cholinesterase by oximes. Biochem Pharmacol. 1978; 27(5):757-61. DOI: 10.1016/0006-2952(78)90516-6. View

SCHOENE K . Aging of soman-inhibited acetylcholinesterase: inhibitors and accelerators. Biochim Biophys Acta. 1978; 525(2):468-71. DOI: 10.1016/0005-2744(78)90243-7. View

Lipp J, Dola T . comparison of the efficacy of HS-6 versus HI-6 when combined with atropine, pyridostigmine and clonazepam for soman poisoning in the monkey. Arch Int Pharmacodyn Ther. 1980; 246(1):138-48. View

Clement J . Efficacy of pro-PAM (N-methyl-1,6-dihydropyridine-2-carbaldoxime hydrochloride) as a prophylaxis against organophosphate poisoning. Toxicol Appl Pharmacol. 1979; 47(2):305-11. DOI: 10.1016/0041-008x(79)90325-9. View

Kusic R, Boskovic B, VOJVODIC V, Jovanovic D . HI-6 in man: blood levels, urinary excretion, and tolerance after intramuscular administration of the oxime to healthy volunteers. Fundam Appl Toxicol. 1985; 5(6 Pt 2):S89-97. DOI: 10.1093/toxsci/5.6part2.89. View

HEFFRON P, HOBBIGER F . Relationship between inhibition of acetylcholinesterase and response of the rat phrenic nerve-diaphragm preparation to indirect stimulation at higher frequencies. Br J Pharmacol. 1979; 66(2):323-9. PMC: 2043639. DOI: 10.1111/j.1476-5381.1979.tb13683.x. View

Shih T . Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats. Arch Toxicol. 1993; 67(9):637-46. DOI: 10.1007/BF01974071. View

10.

van Helden H, van der Wiel H, de Lange J, Busker R, Melchers B, Wolthuis O . Therapeutic efficacy of HI-6 in soman-poisoned marmoset monkeys. Toxicol Appl Pharmacol. 1992; 115(1):50-6. DOI: 10.1016/0041-008x(92)90366-z. View

11.

Hamilton M, Lundy P . HI-6 therapy of soman and tabun poisoning in primates and rodents. Arch Toxicol. 1989; 63(2):144-9. DOI: 10.1007/BF00316437. View

12.

Tattersall J . Ion channel blockade by oximes and recovery of diaphragm muscle from soman poisoning in vitro. Br J Pharmacol. 1993; 108(4):1006-15. PMC: 1908129. DOI: 10.1111/j.1476-5381.1993.tb13498.x. View

13.

DE JONG L, Wolring G . Stereospecific reactivation by some Hagedorn-oximes of acetylcholinesterases from various species including man, inhibited by soman. Biochem Pharmacol. 1984; 33(7):1119-25. DOI: 10.1016/0006-2952(84)90523-9. View

14.

DE JONG L, Wolring G . Reactivation of acetylcholinesterase inhibited by 1,2,2'-trimethylpropyl methylphosphonofluoridate (soman) with HI-6 and related oximes. Biochem Pharmacol. 1980; 29(17):2379-87. DOI: 10.1016/0006-2952(80)90273-7. View

15.

Boskovic B . The treatment of Soman poisoning and its perspectives. Fundam Appl Toxicol. 1981; 1(2):203-13. DOI: 10.1016/s0272-0590(81)80059-0. View

16.

MEETER E, Wolthuis O . The spontaneous recovery of respiration and neuromuscular transmission in the rat after anticholinesterase poisoning. Eur J Pharmacol. 1968; 2(5):377-86. DOI: 10.1016/0014-2999(68)90189-1. View

17.

Puu G, Artursson E, Bucht G . Reactivation of nerve agent inhibited human acetylcholinesterases by HI-6 and obidoxime. Biochem Pharmacol. 1986; 35(9):1505-10. DOI: 10.1016/0006-2952(86)90116-4. View

18.

Clement J, Lee M, Simons K, Briggs C . Pharmacokinetics of the acetylcholinesterase oxime reactivator, HI-6, in rhesus monkeys (Macaca mulatta): effect of atropine, diazepam, and methoxyflurane anesthesia. Biopharm Drug Dispos. 1990; 11(3):227-32. DOI: 10.1002/bdd.2510110307. View

19.

Massoulie J, Bon S . The molecular forms of cholinesterase and acetylcholinesterase in vertebrates. Annu Rev Neurosci. 1982; 5:57-106. DOI: 10.1146/annurev.ne.05.030182.000421. View

20.

Stalc A, Sentjurc M . A contribution to the mechanism of action of SAD-128. Biochem Pharmacol. 1990; 40(11):2511-7. DOI: 10.1016/0006-2952(90)90093-z. View