Abstract
Respiratory insufficiency has long been recognized as the primary cause of death following acute exposure to lethal doses of organophosphorus compounds (OP’s) (deCandole et al., 1953; Holmes, 1952; 1953a; 1953b; Stewart and Anderson, 1968; Wright, 1954; for review, see Brimblecombe, 1977). The highly toxic organophosphorus chemical warfare (CW) nerve agents soman (GD), sarin (GB), tabun (GA), and VX are potent inhibitors of acetylcholinesterase (AChE) and produce complex and widespread toxic effects throughout the body. Within the identifiable confines of the respiratory system alone, the pervasiveness of CW agents’ toxic effects has been noted in a variety of respiratory-related organs and tissues. Early research established that AChE inhibitors are capable of either respiratory facilitation or inhibition in a dose-dependent fashion, that these effects might be attributable to the accumulation of acetylcholine (ACh), and that their sites of action could be in the central nervous system (CNS), the periphery, or both.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abbrecht, P.H., Bryant, H.J., and Kyle, R., 1985, Cardiopulmonary responses and effects of transtracheal jet ventilation following soman administration in dogs, in: “Abstracts from the Fifth Annual Bioscience Review”, Columbia, MD, 29–31 May.
Adams, G.K., Yamamura, H.I. and O’Leary, J.F., 1976, Recovery of central respiratory function following anticholinesterase intoxication, Europ. J. Pharmacol., 38: 101–112.
Bay, E., Adams, N.L., von Bredow, J.K.D. and Nelson, J.D., 1973, Respiratory phase shift of pattern in the medullary reticularformation after soman in the cat, Brain Res., 60: 526–532.
Bradley, P.B., Dhawan, B.N., and Wolstencroft, J.H., 1966, Pharmacological properties of cholinoceptive neurons in the medulla and pons of the cat, J. Physiol.(London), 183: 658–674.
Brimblecombe, R.W., 1977, Drugs acting on central cholinergic mechanisms and affecting respiration, Pharmacol. Ther., 3: 65–74.
Clement, J.G., 1981, Toxicology and pharmacology of bis-pyridinium oximes: Insight into the mechanism of action vs soman poisoning In vivo, Fund. Appl. Toxicol., 1: 193–202.
Clement, J.G., 1982, HI-6: Reactivation of central and peripheral acetylcholinesterase following inhibition by soman, sarin and tabun in vivo in the rat, Biochem. Pharmacol., 31: 1283–1287.
deCandole, C.A., Douglas, W.W., Lovatt-Evans, C., Holmes, R., Spencer, K.E.V., Torrance, R.W. and Wilson, K.M., 1953, The failure of respiration in death by anticholinesterase poisoning, Br. J. Pharmacol. Chemother., 8: 466–475.
Douglas, W.W. and Matthews, P.B.C., 1952, Acute tetraethyl pyrophosphate poisoning in cats and its modification by atropine, J. Physiol. (London), 116: 202–218.
Freeman, A.M. and Himwich, H.E., 1949, DFP: Site of injection and variation in response, Am. J. Physiol., 156: 125–128.
Gordon, J.J., Leadbeater, L. and Maidment, M.P., 1978, The protection of animals against organophosphate poisoning by treatment with a carbamate, Toxicol. Appl. Pharmacol., 43: 207–216.
Heymans, C. and Jacob, J., 1947, Sur la pharmacologies du diisopropylfluorophosphonate (DFP) et le role des cholinesterases. Arch. Int. Pharmacodyn. Ther., 233–252.
Holmes, R., 1952, The mechanism of respiratory failure in the rabbit poisoned with GB, personal communication with author.
Holmes, R., 1953a, The effects of GB on the respiration of monkeys, personal communication with author.
Holmes, R., 1953b, The cause of death from acute anticholinesterase poisoning in the rabbit, cat and monkey, personal communication with author.
Holmstedt, B., 1959, Pharmacology of organophosphorus cholinesterase inhibitors, Pharmacol Rev., 11: 567–688.
Johanson, W.G., Anzueto, A., Berdine, G.G., Moore, G.T. and White, C.D., 1985, Etiology of respiratory failure in organophosphate intoxication in nonhuman primates, in: “Abstracts from the Fifth Annual Bioscience Review”, Columbia, MD, 29–31 May.
Johanson, W.G., Anzueto, A., Berdine, G.G., Moore, G.T. and White, C.D., 1985, Ventilatory support of organophosphate intoxication in nonhuman primates, in: “Abstracts from the Fifth Annual Bioscience Review”, Columbia, MD, 29–31 May.
Karczmar, A.G., 1967, Pharmacologic, toxicologic, and therapeutic properties of anticholinesterase agents, Physiol. Pharmacol., 3: 163–322.
Kirsten, E.B., Satayavivad, J., St. John, W.M., and Wang, S.C., 1978, Alteration of medullary respiratory unit discharge by iontophoretic application of putative neurotransmitters, Br. J. Pharmacol., 63: 275–281.
Koelle, G.B. and Gilman, A., 1949, Anticholinesterase drugs, J. Pharmacol. Exp. Ther., 95: 166–216.
Krivoy, W.A., Hart, E.R. and Marrazzi, A.S., 1951, Further analysis of the actions of DFP and curare on the respiratory center, J. Pharmacol. Exp. Ther., 103: 351–364.
Lipp, J. and Dola, T., 1980, Comparison of HS-6 versus HI-6 when combined with atropine, pyridostigmine and clonazepam for soman poisoning in the monkey, Arch. Int. Pharmacodyn. Ther., 246: 138–148.
Lovatt-Evans, C., 1951, Neuromuscular block by anticholinesterases, J. Physiol.(London), 114: 6 P.
Lundy. P.M., 1978, The ganglionic blocking properties of the cholinesterase reactivator HS-6, Can. J. Physiol. Pharmacol., 56: 857–862.
Lundy, P.M. and Shih, T.-M., 1983, Examination of the role of central cholinergic mechanisms in the therapeutic effects of HI-6 in organophosphate poisoning, J. Neurochem., 40: 1321–1328.
Lundy, P.M. and Tremblay, K., 1979, Ganglionic blocking properties of some bispyridinium soman antagonists, Europ. J. Pharmacol., 60: 47–53.
Maksimovic, M., Boskovic, B., Radovic, L j., Tadic, V., Deljac, V. and Binenfeld, Z., 1980, Antidotal effects of bispyridinium-2-monooxime carbonyl derivatives in intoxications with highly toxic organophosphorus compounds, Acta Pharm. Jugosl., 30: 151–160.
McNamara, B.P., Koelle, G.B. and Gilman, A., 1946, The treatment of diisopropylfluorophosphate (DFP) poisoning in rabbits, J. Pharmacol. Exp. Ther., 88: 27–33.
Meeter, E. and Wolthuis, O.L., 1968, The spontaneous recovery of respiration and neuromuscular transmission in the rat after anticholinesterase poisoning, Europ. J. Pharmacol., 2: 377–386.
Modell, W. and Krop, S., 1946, Antidotes to poisoning by diisopropylfluorophosphate in cats, J. Pharmacol. Exp. Ther., 88: 34–38.
Modell, W., Krop, S., Hitchcock, P. and Riker, W.F., 1946, General systemic actions of diisopropylfluorophosphate (DFP) in cats, J. Pharmacol. Exp. Ther., 87: 400–413.
Muir, A.W., French, M.C. and Ians, R.H., 1975, Changes in physiological response and cholinesterase level in rabbits poisoned with sarin, soman and a quaternary V agent (T2394), personal communication with author.
Rickett, D.L., Glenn, J.F., Foster, R.E., Traub, R.K. and Beers, E.T., 1984, Differentiation of medullary and neuromuscular actions of nerve agents, in: “Proceedings of the Symposium on Respiratory Care of Chemical Casualties”, H.H. Newball, ed., USAMRDC.
Salmoiraghi, G.C. and Steiner, F.A., 1963, Acetylcholine sensitivity of cat’s medullary neurons, J. Neurophysiol., 26: 581–597.
Schaumann, W. and Job, C., 1958, Differential effects of a quaternary cholinesterase inhibitor, phospholine, and its tertiary analog, compound 217-A0, on central control of respiration and on neuromuscular transmission. The antagonism by 217-A0 of respiratory arrest caused by morphine, J. Pharmacol. Exp. Ther., 123: 114 - 120.
Schenk, J., Loffler, W. and Weger, N., 1976, Therapeutic effects of HS-3, HI-6, benactyzine and atropine in soman poisoning of dogs, Arch. Toxicol., 36: 71–81.
Shih, T.-M., Whalley, C.E., Valdes, J.J., Lundy, P.M. and Lockwood, P.A., 1985, Cholinergic effects of HI-6 in soman poisoning, in: “Dynamics of Cholinergic Function”, I. Hanin, ed., Plenum Press, New York, NY.
Smolders, F.D.J., Folgering, H-Th.M., 1979, Description of the firing pattern of respiratory neurons by frequency modulated interspike interval distributions, Pflugers Archiv, 383: 1–8.
Stewart, W.C., 1959, The effects of sarin and atropine on the respiratory center and neuromuscular junctions of the rat, Can. J. Biochem. Physiol., 37: 651–660.
Stewart, W.C. and Anderson, E.A., 1968, Effects of a cholinesterase inhibitor when injected into the medulla of the rabbit, J. Pharmacol Exp. Ther., 162: 309–318.
Verbeke, R., 1949, Nouvelles contributions a la pharmacologic du diisopropylfluorophosphonate (DFP), Arch. Int. Pharmacodyn. Ther., 79: 1–31.
Wolthuis, O.L., Berends, F. and Meeter, E., 1981, Problems in the therapy of soman poisoning, Fund. Appl. Toxicol., 1: 183–192.
Wolthuis, O.L. and Kepner, L.A., 1978, Successful oxime therapy one hour after soman intoxication in the rat, Europ. J. Pharmacol., 49: 415–425.
Wright, P.G., 1954, An analysis of the central and peripheral components of respiratory failure produced by anticholinesterase poisoning in the rabbit, J. Physiol.(London), 126: 52–70.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 Plenum Press, New York
About this chapter
Cite this chapter
Rickett, D.L., Beers, E.T. (1987). Differentiation of Medullary and Neuromuscular Effects of Nerve Agents. In: Dun, N.J., Perlman, R.L. (eds) Neurobiology of Acetylcholine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5266-2_42
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5266-2_42
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5268-6
Online ISBN: 978-1-4684-5266-2
eBook Packages: Springer Book Archive