Neurobiology of Acetylcholine pp 535-550 | Cite as
Differentiation of Medullary and Neuromuscular Effects of Nerve Agents
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.
Keywords
Phrenic Nerve Respiratory Arrest Nerve Agent Organophosphorus Compound Diaphragm MusclePreview
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.Google Scholar
- 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.CrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.Google Scholar
- Brimblecombe, R.W., 1977, Drugs acting on central cholinergic mechanisms and affecting respiration, Pharmacol. Ther., 3: 65–74.Google Scholar
- 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.CrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.Google Scholar
- 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.Google Scholar
- Freeman, A.M. and Himwich, H.E., 1949, DFP: Site of injection and variation in response, Am. J. Physiol., 156: 125–128.Google Scholar
- 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.PubMedCrossRefGoogle Scholar
- Heymans, C. and Jacob, J., 1947, Sur la pharmacologies du diisopropylfluorophosphonate (DFP) et le role des cholinesterases. Arch. Int. Pharmacodyn. Ther., 233–252.Google Scholar
- Holmes, R., 1952, The mechanism of respiratory failure in the rabbit poisoned with GB, personal communication with author.Google Scholar
- Holmes, R., 1953a, The effects of GB on the respiration of monkeys, personal communication with author.Google Scholar
- Holmes, R., 1953b, The cause of death from acute anticholinesterase poisoning in the rabbit, cat and monkey, personal communication with author.Google Scholar
- Holmstedt, B., 1959, Pharmacology of organophosphorus cholinesterase inhibitors, Pharmacol Rev., 11: 567–688.PubMedGoogle Scholar
- 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.Google Scholar
- 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.Google Scholar
- Karczmar, A.G., 1967, Pharmacologic, toxicologic, and therapeutic properties of anticholinesterase agents, Physiol. Pharmacol., 3: 163–322.Google Scholar
- 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.PubMedGoogle Scholar
- Koelle, G.B. and Gilman, A., 1949, Anticholinesterase drugs, J. Pharmacol. Exp. Ther., 95: 166–216.PubMedGoogle Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- Lovatt-Evans, C., 1951, Neuromuscular block by anticholinesterases, J. Physiol.(London), 114: 6 P.Google Scholar
- Lundy. P.M., 1978, The ganglionic blocking properties of the cholinesterase reactivator HS-6, Can. J. Physiol. Pharmacol., 56: 857–862.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- Lundy, P.M. and Tremblay, K., 1979, Ganglionic blocking properties of some bispyridinium soman antagonists, Europ. J. Pharmacol., 60: 47–53.CrossRefGoogle Scholar
- 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.Google Scholar
- 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.PubMedGoogle Scholar
- 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.CrossRefGoogle Scholar
- Modell, W. and Krop, S., 1946, Antidotes to poisoning by diisopropylfluorophosphate in cats, J. Pharmacol. Exp. Ther., 88: 34–38.PubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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.Google Scholar
- 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.Google Scholar
- Salmoiraghi, G.C. and Steiner, F.A., 1963, Acetylcholine sensitivity of cat’s medullary neurons, J. Neurophysiol., 26: 581–597.PubMedGoogle Scholar
- 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.PubMedGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.Google Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar
- 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.PubMedGoogle Scholar
- Verbeke, R., 1949, Nouvelles contributions a la pharmacologic du diisopropylfluorophosphonate (DFP), Arch. Int. Pharmacodyn. Ther., 79: 1–31.PubMedGoogle Scholar
- Wolthuis, O.L., Berends, F. and Meeter, E., 1981, Problems in the therapy of soman poisoning, Fund. Appl. Toxicol., 1: 183–192.CrossRefGoogle Scholar
- 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.CrossRefGoogle Scholar
- 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.Google Scholar