Neurotoxins with anticholinesterase activity and their possible use as warfare agents;Neurotoxinas con actividad anticolinesterásica y su posible uso como agentes de guerra

Medicina Clinica

Volumn 121, Issue 13, 2003, Pages 511-517

  Pita, René ^a,b   Anadón, Arturo ^b   Martínez Larrañaga, María Rosa ^b  

^a Escuela Militar de Defensa NBQ   (Spain)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

Author keywords

Anatoxin a(s); Biological warfare agents; Chemical warfare agents; Fasciculins; Nerve agents; Neurotoxins; Onchidal; Toxins

Indexed keywords

ANATOXIN A; CHEMICAL WARFARE AGENT; CHOLINESTERASE INHIBITOR; FASCICULIN; INDUSTRIAL CHEMICAL; NEUROTOXIN; ONCHIDAL; ORGANOPHOSPHATE INSECTICIDE; SARIN; SOMAN; UNCLASSIFIED DRUG;

AEROSOL; BIOLOGICAL WARFARE; CHEMICAL WARFARE; CHOLINERGIC ACTIVITY; CLINICAL FEATURE; HUMAN; NEUROTOXICITY; REVIEW; SYMPTOM; TERRORISM;

EID: 0242467774     PISSN: 00257753     EISSN: None     Source Type: Journal    
DOI: 10.1157/13053143     Document Type: Review

References (82)

1. Alibek K, Handelman S. Biohazard. New York: Random House, 1999.
2. Pearson GS. The UNSCOM saga: chemical and biological weapons nonproliferation. London: Macmillan Press, 1999.
3. Stern J. The ultimate terrorists. Massachusetts: Harvard University Press, 1999.
4. Birstein VJ. The perversion of knowledge: the true story of Soviet science. Colorado: Westview Press, 2001.
5. Instrumento de ratificación del Convenio sobre la prohibición del desarrollo, la producción y el almacenamiento de armas bacteriológicas (biológicas) y toxínicas y sobre su destrucción, hecho en Londres, Moscú y Washington el 10 de abril de 1972. BOE n.° 165, 11 de julio de 1979.
6. Instrumento de ratificación de la Convención sobre la prohibición del desarrollo, la producción, el almacenamiento y el empleo de armas químcas y sobre su destrucción, hecho en París el 13 de enero de 1993. BOE n° 300, 13 de diciembre de 1996.
7. Corrección de errores del instrumento de ratificación de la Convención sobre la prohibición del desarrollo, la producción, el almacenamiento y el empleo de armas químicas y sobre su destrucción, hecho en París el 13 de enero de 1993. BOE n.° 163, 9 de julio de 1997.
8. Organización del Tratado del Atlántico Norte (OTAN). NATO handbook on the medical aspects of NBC defensive operations part 2: biological. 4th ed. NATO, 1996.
9. Pita R, Anadón A, Martínez-Larrañaga MR. Actualización de las intoxicaciones por agentes neurotóxicos de guerra: efectos fisiopatológicos (1). Aten Farm 2002;4:98-116.
10. Bernhard SA, Orgel LE. Mechanism of enzyme inhibition by phosphate esters. Science 1959;130:625-6.
11. Millard CB, Kryger G. Ordentlich A, Greenblatt HM, Harel M, Raves ML, et al. Crystal structures of aged phosphonylated acetycholinesterase: nerve agent reaction products at the atomic level. Biochemistry 1999;38:7032-9.
12. Grob D, Harvey AM. The effects and treatment of nerve gas poisoning. Am J Med 1953;14:52-63
13. Berry WK, Davies DR. Factors influencing the rate of «aging» of a series of alkyl methylphosphonyl-acetylcholinesterases. Biochem J 1966;100:572-6.
14. Spencer PS, Wilson BW, Albuquerque EX. Sarin, other «nerve agents» and their antidotes. En: Spencer PS, Schaumburg HH, Ludolph AC, editors. Experimental and clinical neurotoxicology. 2nd ed. New York: Oxford University Press, 2000; p. 1073-93.
15. Pita R, Anadón A, Martinez-Larrañaga MR. Actualización de las intoxicaciones por agentes neurotóxicos de guerra: tratamiento farmacológico (2). Aten Farm 2002;4:178-88.
16. Pita R, Anadón A, Martínez-Larrañaga MR. Estado actual del pretratamiento de las intoxicaciones por agentes neurotóxicos de guerra con piridostigmina y otras arlernativas farmacológicas. Rev Toxicol 2003;20:1-7.
17. Schaumburg HH. Human neurotoxic disease. En: Spencer PS, Schaumburg HH, Ludolph AC, editors. Experimental and clinical neurotoxicology. 2nd ed. New York: Oxford University Press, 2000: p. 55-82.
18. Marrs TC, Maynard RL, Sidell FR. Organophosphate nerve agents. En: Marrs TC, Maynard RL, Sidell FR, editors. Chemical warfare agents: toxicology and treatment. Chichester: John Wiley & Sons, 1996.
19. Mahmood NA, Carmichael WW. The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flosaquae NRC 525-17. Toxicon 1986;24:425-34.
20. Hyde EG, Carmichael WW. Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7). J Biochem Toxicol 1991;6:195-201.
21. Cook WO, Beasley VR, Lovell RA, Dahlem AM, Hooser SB, Mahmood NA, et al. Consistent inhibition of peripheral cholinesterases by neurotoxins from the freshwater cyanobacterium Anabaena flos-aquae: studies of ducks, swine, mice and a steer. Environ Toxicol Chem 1989;8:915-22.
22. Cook WO, Beasley VR, Dahlem AM, Dellinger JA, Harlin KS, Carmichael WW. Comparison of effects of anatoxin-a(s) and paraoxon, physostigmine and pyridostigmine on mouse brain cholinesterase activity. Toxicon 1988;26:750-3.
23. Cook WO, Dellinger JA, Singh SS, Dahlem AM, Carmichael WW, Beasley VR. Regional brain cholinesterase activity in rats injected intraperitoneally with anatoxin-a(s) or paraoxon. Toxicol Lett 1989;49:29-34.
24. Cook WO, Iwamoto GA, Schaeffer DJ, Beasley VR, Carmichael WW. Effect of anatoxin-a(s) from Anabaena flos-aquae NRC-525-17 on blood pressure, heart rate, respiratory rate, tidal volume, minute volume, and phrenic nerve activity in rats. J Environ Pathol Toxicol Oncol 1989;9:393-400.
25. Cook WO, Iwamoto GA, Schaeffer DJ, Carmichael WW, Beasley VR. Pathophysiologic effects of anatoxin-a(s) in anaesthetized rats: the influence of atropine and artificial respiration. Pharmacol Toxicol 1990;67:151-5.
26. Karlsson E, Mbugua PM, Rodríguez-Ithurralde D. Fasciculins, anticholinesterase toxins from the venom of the green mamba Dendroaspis angusticeps. J Physiol (Paris) 1984;79:232-40.
27. 125I-fasciculin to rat brain acetylcholinesterase: the complex still binds diisopropyl fluorophosphate. J Biol Chem 1993;268:12458-67.
28. Lin WW, Lee CY, Carlsson FHH, Joubert FJ. Anticholinesterase activity of angusticeps-type toxins and protease inbibitor homologues from mamba venoms. Asia Pac J Pharmacol 1987;2:79-85.
29. Puu G, Koch M. Comparison of kinetic parameters for acetylthiocholine, soman, ketamine and fasciculin towards acetylcholinesterase in liposomes and in solution. Biochem Pharmacol 1990;40:2209-14.
30. Durán R, Cerveñansky C, Dajas F, Tipton KF. Fasciculin inhibition of acetylcholinesterase is prevented by chemical modification of the enzyme at a peripheral site. Biochim Biophys Acta 1994;1201:381-8.
31. Radic Z, Durán R, Vellom DC, Li Y, Cerveñansky C, Taylor P. Site of fasciculin interaction with acetylcholinesterase. J Biol Chem 1994;269:11233-9.
32. Bourne Y, Taylor P, Marchot P. Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex. Cell 1995;83:503-12.
33. Harel M, Kleywegt GJ, Ravelli RBG, Silman I, Sussman JL. Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target. Structure 1995;3:1355-66.
34. 7 isolated from eastern green mamba venom. Toxicon 1986;24:33-40.
35. Abramson SN, Radic Z, Manker D, Faulkner DJ, Taylor P. Onchidal: a naturally occurring irreversible inhibitor of acetylcholinesterase with a novel mechanism of action. Mol Pharmacol 1989;36:349-54.
36. Carmichael WW. Cyanobacteria secondary metabolites: the cyanotoxins. J Appl Bacteriol 1992;72:445-59
37. Park HD, Watanabe MF, Harda K, Nagai H, Suzuki M, Watanabe M, et al. Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters. Nat Toxins 1993;1:353-60.
38. Spivak CE, Witkop B, Albuquerque EX. Anatoxin-a: a novel, potent agonist at the nicotinic receptor. Mol Pharmacol 1980:18:384-94.
39. Molloy L, Wonnacott S, Gallagher T, Brough PA, Livett BG. Anatoxin-a is a potent agonist of the nicotinic acetylcholine receptor of bovine adrenal chromaffin cells. Eur J Pharmacol 1995;289:447-53.
40. Wonnacott S, Swanson KL, Albuquerque EX, Huby NJS, Thompson P, Gallagher T. Homoanatoxin: a potent analogue of anatoxin-a. Biochem Pharmacol 1992;43:419-23.
41. Skulberg OM, Carmichael WW, Andersen RA, Matsunaga S, Moore RE, Skulberg R. investigations of a neurotoxic oscillatorialean strain (Cyanophyceae) and its toxin: isolation and characterization of homoanatoxin-a. Environ Toxicol Chem 1992;11:321-9.
42. Lilleheil G, Andersen RA, Skulberg OM, Alexander J. Effects of a homoanatoxin-a containing extract from Oscillatoria formosa (Cyanophyceael/ cyanobacteria) on neuromuscular transmission. Toxicon 1997;35:1275-89.
43. Matsunaga S, Moore RE, Niemczura WP, Carmichael WW. Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae. J Am Chem Soc 1989;111:8021-3.
44. Gorham PR, McLachlan J, Hammer UT, Kim WK. Isolation and culture of toxic strains of Anabaena flos-aquae (Lyngb.) de Bréb. Verh Internat Verein Limnol 1964;15:796-804.
45. Devlin JP, Edwards OE, Gorham PR, Hunter NR, Pike RK, Stavric B. Anatoxin-a, a toxic alkaloid from Anabaena flos-aquae NRC-44h. Can J Chem 1977;55:1367-71.
46. Henriksen P, Carmichael WW, An J, Moestrup Ø. Detection of an anatoxin-a(s)-like anticholinesterase in natural blooms and cultures of cyanobacteria/blue-green algae from Danish lakes and in the stomach contents of poisoned birds Toxicon 1997;35:901-13.
47. Onodera H, Oshima Y, Henriksen P, Yasumoto T. Confirmation of anatoxin-a(s), in the cyanobacterium Anabaena lemmermannii, as the cause of bird kills in Danish lakes. Toxicon 1997;35:1645-8.
48. Moore BS, Ohtani I, De Koning CB, Moore RE, Carmichael WW. Biosynthesis of anatoxin-a(s): origin of the carbons. Tetrahedron Lett 1992;33:6595-8.
49. Hemscheidt T, Burgoyne DL, Moore RE. Biosynthesis of anatoxin-a(s). (2S,4S)-4-hydroxyarginine as an intermediate. J Chem Soc Chem Commun 1995:205-6.
50. Mahmood NA, Carmichael WW. Anatoxin-a(s), an anticholinesterase from the cyanobacterium Anabaena flos-aquae NRC-525-17. Toxicon 1987;25:1221-7.
51. Cook WO, Dahlem AM, Harlin KS, Beasley VR, Hooser SB, Haschek WM, et al. Reversal of cholinesterase inhibition and clinical signs and the postmortem findings in mice after intraperitoneal administration of anatoxin-a(s), paraoxon or pyridostigmine. Vet Hum Toxicol 1991;33:1-4.
52. Mahmood NA, Carmichael WW, Pfahler D. Anticholinesterase poisonings in dogs from a cyanobacterial (blue-green algae) bloom dominated by Anabaena flos-aquae. Am J Vet Res 1988;49:500-3.
53. Jolkkonen M. Muscarinic toxins from Dendroaspis (mamba) venom: peptides selective for subtypes of muscarinic acetylcholine receptors [tesis doctoral]. Uppsala: Uppsala University, 1996.
54. Strydom DJ. Snake venom toxins: purification and properties of low-molecular-weight polypeptides of Dendroaspis polylepis polylepis (black mamba) venom. Eur J Biochem 1976;69:169-76.
55. Ludolph AC. Mamba snake venom. En: Spencer PS, Schaumburg HH, Ludolph AC, editors. Experimental and clinical neurotoxicology. 2nd ed. New York: Oxford University Press, 2000; p. 751.
56. Hawgood B, Bon C. Snake venom presynaptic toxins. En: Tu AT, editor. Handbook of natural toxins volume 5: reptile venoms and toxins. New York: Marcel Dekker, 1991; p. 3-52.
57. Tu AT. Neurotoxins from snake venoms. En: Chang LW, Dyer RS, editors. Handbook of neurotoxicology. New York: Marcel Dekker, 1995; p. 637-65.
58. Rodríguez-Ithurralde D, Silveira R, Barbeito L, Dajas F. Fasciculin, a powerful anticholinesterase polypeptide from Dendroaspis angusticeps venom Neurochem Int 1983;5:267-74.
59. VII from Dendroaspis angusticeps venom. J Biol Chem 1973;248:4915-9.
60. Cerveñansky C, Engström Å, Karlsson E. Role of arginine residues for the activity of fasciculin. Eur J Biochem 1995;229:270-5
61. Joubert FJ, Taljaard N. The complete primary structure of toxin C from Dendroaspis polylepis polylepis (black mamba) venom. S Afr J Chem 1978;31:107-10
62. le Du MH, Marchot P, Bougis PE, Fontecilla-Camps JC. 1.9-Å resolution structure of fasciculin 1, an anti-acetylcholinesterase toxin from green mamba snake venom. J Biol Chem 1992;267:22122-30.
63. Sussman JL, Harel M, Frolow F, Oefner C, Goldman A, Toker L, et al. Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 1991;253:872-9.
64. Harel M, Schalk I, Ehret-Sabatier L, Bouet F, Goeldner M, Hirth C, et al. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc Natl Acad Sci USA 1993;90:9031-5.
65. Rosenberry TL, Rabl CR, Neumann E. Binding of the neurotoxin fasciculin 2 to the acetylcholinesterase peripheral site drastically reduces the association and dissociation rate constants for N-methylacridinium bin ding to the active site. Biochemistry 1996;35:685-90.
66. Quillfeldt J, Raskovsky S, Dalmaz C, Dias M, Huang C, Netto CA, et al. Bilateral injection of fasciculin into the amygdala of rats: effects on two avoidance tasks, acetylcholinesterase activity, and cholinergic mucarinic receptors. Pharmacol Biochem Behav 1990;37:439-44.
67. Dajas F, Bolioli B, Castelló ME, Silveira R. Rat striatal acetylcholinesterase inhibition by fasciculin (a polypeptide from green mamba snake venom). Neurosci Lett 1987;77:87-91.
68. Bolioli B, Castelló ME, Jerusalinsky D, Rubinstein M, Medina J, Dajas F. Neurochemical and behavioral correlates of unilateral striatal acetylcholinesterase inhibition by fasciculin in rats. Brain Res (Netherlands) 1989;504:1-6.
69. Young CM, Greenwood PG, Powell CJ. The ecological role of defensive secretions in the intertidal pulmonate Onchidella borealis. Biol Bull 1986;171:391-404.
70. Ireland C, Faulkner DJ. The defensive secretion of the opisthobranch mollusc Onchidella binneyi. Bioorg Chem 1978;7:125-31.
71. Walsh CT. Suicide substrates, mechanism-based enzyme inactivators: recent developments. Annu Rev Biochem 1984;53:493-535.
72. Baker R, Briner PH, Evans DA. Chemical defence in the termite Ancistrotermes cavithorax: ancistrodial and ancistrofuran. J Chem Soc Chem Commun 1978:410-1.
73. Jonassohn M. Sesquiter penoid unsaturated dialdehydes: structural properties that affect reactivity and bioactivity [tesis doctoral]. Lund: Lund University, 1996.
74. Suárez S, Hickey AJ. Drug properties affecting aerosol behavior. Respir Care 2000;45:652-66.
75. Nozaki H, Hori S, Shinozawa Y, Fujishima S, Takuma K, Sagoh M, et al. Secondary exposure of medical staff to sarin vapor in the emergency room. Intensive Care Med 1995;21:1032-5.
76. Organización del Tratado del Atlántico Norte (OTAN). NATO handbook on the medical aspects of NBC defensive operations part 3: chemical. 4th ed. NATO, 1996.
77. Nakajima T, Sato S, Morita H, Yanagisawa N. Sarin poisoning of a rescue team in the Matsumoto sarin incident in Japan. Occup Environ Med 1997:54:697-701.
78. Okudera H, Morita H, Iwashita T, Shibata T, Otagiri T, Kobayashi S, et al. Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism. Am J Emerg Med 1997;15:527-8.
79. Okumura T, Suzuki K, Fukuda A, Kohama A, Takasu N, Ishimatsu S, et al. The Tokyo subway sarin attack: disaster management, part 2: hospital response. Acad Emerg Med 1998;5:618-24.
80. Okudera H. Clinical features on nerve gas terrorism in Matsumoto. J Clin Neurosci 2002;9:17-21.
81. Koch BL, Edvinsson ÅA, Koskinen LD. Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs. J Appl Toxicol 1999;19:19-23.
82. Organización del Tratado del Atlántico Norte (OTAN). NATO handbook for sampling and identification of biological and chemical agents volume 1: procedures and techniques. 5th ed. NATO, 2000.