Cyanide as a Weapon of Terror

Rotenberg, Joshua S.

doi:10.3928/0090-4481-20030401-07

Cited by 28 publications

(9 citation statements)

References 11 publications

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“…Treatments for cyanide poisoning are many, which should be instituted immediately and aggressively for optimal results (Baud, 2007;Bhattacharya & Flora, 2009;Rotenberg, 2003). However, most of the treatments suffer from serious limitations (Bhattacharya, 2000;Van Heijst et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Accelerated stability and bioassay of a new oralα-ketoglutarate formulation for treating cyanide poisoning

Bhattacharya

Gopalan

Singh

et al. 2013

Pharmaceutical Biology

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Context: Due to several limitations of existing cyanide antidotes, a-ketoglutarate (a-KG) has been proposed as a promising treatment for cyanide. Objective: This study reports the accelerated stability and bioassay of a new oral a-KG formulation. Materials and methods: Amber-colored PVDF bottles containing 100 ml of 10% a-KG in 70% sorbitol, preservative (sodium methyl paraben and sodium propyl paraben), sweetener (sodium saccharine), flavor (American ice-cream soda and peppermint) and color (tartrazine), at pH 7.0-8.0 were stored in stability chamber (40 AE 2 C and 75 AE 5% humidity) for 6 months in a GMP compliant facility. Various physical (pH, color, evaporation, extractable volume and clarity), chemical (identification and quantification of active ingredient) and microbiological (total aerobic count) analyses, together with protection studies were carried periodically in mice. Acute toxicity of the formulation and bioavailability of a-KG were assessed in rats at the beginning of the experiment. Results: No physical changes and microbiological growth were observed in the formulation. After 6 months, a-KG content in the formulation diminished by $24% but its protective efficacy against cyanide remained at 5.9-fold. Protection was further characterized spectrophotometrically by disappearance of a-KG spectrum in the presence of cyanide, confirming cyanohydrin formation. Oral LD 50 of a-KG formulation in rats was 47.0 g/kg body weight, and did not produce any acute toxicity of clinical significance. Also, an appreciable amount of a-KG was measured in blood. Conclusion: As per the guidelines of International Conference on Harmonization, the new a-KG formulation exhibited satisfactory stability, bioefficacy and safety as cyanide antidote.

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Section: Discussionmentioning

confidence: 99%

Accelerated stability and bioassay of a new oralα-ketoglutarate formulation for treating cyanide poisoning

Bhattacharya

Gopalan

Singh

et al. 2013

Pharmaceutical Biology

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“…[4][5][6][7] Cyanide has been identified as among the highestpriority chemical threats. [8][9][10][11][12][13][14][15][16] Milligram quantities of cyanide can cause convulsions, seizures, cardiovascular collapse, and death in minutes, and lower doses cause a spectrum of debilitating, long-lasting pathologies, including irreversible neuronal death in select brain areas. 17,18 Unlike many other chemical threats, cyanide is readily accessible in large quantities, making it feasible for terrorists to acquire.…”

Section: The Need For Novel Cyanide Countermeasuresmentioning

confidence: 99%

“…7,8 Cyanide also leads to the generation of reactive oxygen species, including hydroxyl radicals, 9,10 and may itself be converted to the potent free radical of cyanide. 11 Exposure to a lethal dose of cyanide can cause death within minutes, 12 but there are also long-term consequences of sublethal exposure, particularly in the central nervous system, the precise mechanisms for which remain unclear. Short-term memory loss and a Parkinson disease-like syndrome are well reported, and there are also other less welldefined neurological problems in many subjects.…”

Section: Cyanide Mechanismsmentioning

confidence: 99%

A countermeasure development pipeline

MacRae

Boss

Brenner

et al. 2016

Annals of the New York Academy of Sciences

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We have developed an integrated pipeline for countermeasure discovery that, under the auspices of the National Institutes of Health Countermeasures Against Chemical Threats network, is one of the few efforts within academia that by design spans the spectrum from discovery to phase I. The successful implementation of this approach for cyanide would enable efficient proof-of-concept studies that would lay the foundation for a generalizable strategy for parallel mechanistic studies and accelerated countermeasure development in the face of new and emerging chemical threats.

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“…Caution must be taken as hypotension and methemoglobinimia are additional complications. The intravenous dose of sodium thiosulfate is also titrated to hemoglobin level (Rotenberg, 2003b).…”

Section: Nerve Agentsmentioning

confidence: 99%