Development of antidotes for sodium monofluoroacetate (1080)

Christian J. Cook, Charles T. Eason, Mark Wickstrom, Chris D. Devine

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Baits containing sodium monofluoroacetate (1080) are commonly used in New Zealand during feral pest control operations. However, each year, a number of domestic dogs are unintentionally killed during these control operations, and a suitable antidote to 1080 intoxication is required. The primary toxic mechanism of 1080 is well known. However, as with other pathologies where energy deprivation is the main effect of intoxication, the cascade of effects that arises from this primary mechanism is complex. At present, putative antidotes for 1080 are generally unable to address the primary mechanism of intoxication but such agents may be able to control the cascade of secondary effects, which can result during intoxication. Part of the reason for this is that targeting the cascade can provide a longer window of time for antidote success. We have undertaken studies that identified some of the central nervous system (CNS) and systemic pathophysiological cascades caused by 1080 intoxication. Using this information we designed antidotes, on the basis of preventing different steps in this cascade. In the chicken model targeting systemic changes, in particular reducing effects of nitric oxide derivatives generated in cardiac muscle, proved successful in reducing fatality associated with 1080. In rats and sheep, targeting the CNS with a number of compounds including: glutamate; calcium and dopamine antagonists; gamma amino butyric acid agonists, and astressin-like compounds reduced fatalaties. However, to be successful in the rat and sheep model a given antidote needed to move quickly from systemic circulation across the blood brain barrier and into the CNS. The work also suggests ways in which specific biomarkers of 1080 exposure may be developed with respect to different species.

Original languageEnglish
Pages (from-to)72-76
Number of pages5
JournalBiomarkers
Volume6
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Antidotes
Sodium
Neurology
Central Nervous System
Rats
Sheep
Pest control
Pest Control
Butyric Acid
Dopamine Antagonists
Poisons
Biomarkers
Pathology
Blood-Brain Barrier
New Zealand
Muscle
Glutamic Acid
Chickens
Myocardium
Nitric Oxide

Cite this

Cook, C. J., Eason, C. T., Wickstrom, M., & Devine, C. D. (2001). Development of antidotes for sodium monofluoroacetate (1080). Biomarkers, 6(1), 72-76. https://doi.org/10.1080/135475001452814
Cook, Christian J. ; Eason, Charles T. ; Wickstrom, Mark ; Devine, Chris D. / Development of antidotes for sodium monofluoroacetate (1080). In: Biomarkers. 2001 ; Vol. 6, No. 1. pp. 72-76.
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Cook, CJ, Eason, CT, Wickstrom, M & Devine, CD 2001, 'Development of antidotes for sodium monofluoroacetate (1080)', Biomarkers, vol. 6, no. 1, pp. 72-76. https://doi.org/10.1080/135475001452814

Development of antidotes for sodium monofluoroacetate (1080). / Cook, Christian J.; Eason, Charles T.; Wickstrom, Mark; Devine, Chris D.

In: Biomarkers, Vol. 6, No. 1, 2001, p. 72-76.

Research output: Contribution to journalArticle

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AB - Baits containing sodium monofluoroacetate (1080) are commonly used in New Zealand during feral pest control operations. However, each year, a number of domestic dogs are unintentionally killed during these control operations, and a suitable antidote to 1080 intoxication is required. The primary toxic mechanism of 1080 is well known. However, as with other pathologies where energy deprivation is the main effect of intoxication, the cascade of effects that arises from this primary mechanism is complex. At present, putative antidotes for 1080 are generally unable to address the primary mechanism of intoxication but such agents may be able to control the cascade of secondary effects, which can result during intoxication. Part of the reason for this is that targeting the cascade can provide a longer window of time for antidote success. We have undertaken studies that identified some of the central nervous system (CNS) and systemic pathophysiological cascades caused by 1080 intoxication. Using this information we designed antidotes, on the basis of preventing different steps in this cascade. In the chicken model targeting systemic changes, in particular reducing effects of nitric oxide derivatives generated in cardiac muscle, proved successful in reducing fatality associated with 1080. In rats and sheep, targeting the CNS with a number of compounds including: glutamate; calcium and dopamine antagonists; gamma amino butyric acid agonists, and astressin-like compounds reduced fatalaties. However, to be successful in the rat and sheep model a given antidote needed to move quickly from systemic circulation across the blood brain barrier and into the CNS. The work also suggests ways in which specific biomarkers of 1080 exposure may be developed with respect to different species.

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