The Experts below are selected from a list of 5217 Experts worldwide ranked by ideXlab platform
Herbert T. Nagasawa - One of the best experts on this subject based on the ideXlab platform.
-
Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3-Mercaptopyruvate for Intramuscular Administration
Journal of medicinal chemistry, 2013Co-Authors: Steven E. Patterson, Alexandre R. Monteil, Jonathan F. Cohen, Daune L. Crankshaw, Robert Vince, Herbert T. NagasawaAbstract:Current cyanide Antidotes are administered by IV infusion, which is suboptimal for mass casualties. Therefore, in a cyanide disaster, intramuscular (IM) injectable Antidotes would be more appropriate. We report the discovery of the highly water-soluble sulfanegen triethanolamine as a promising lead for development as an IM injectable cyanide antidote.
-
A novel paradigm for assessing efficacies of potential Antidotes against neurotoxins in mice.
Toxicology Letters, 2007Co-Authors: Daune L. Crankshaw, Steven E. Patterson, David J. W. Goon, Jacquie E. Briggs, David Delong, Michael A. Kuskowski, Herbert T. NagasawaAbstract:Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD50 for cyanide elicited by the Antidotes. This required the use of high doses of cyanide following pretreatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD50 determinations: we developed a new test paradigm that allowed for maximal survival of cyanide-treated animals with greatly reduced numbers of animals. Symptoms of cyanide toxicity include disruption of neuromuscular coordination, i.e., the righting reflex. Therefore, to establish a dose-response curve, the times required for recovery of this righting reflex with increasing doses of cyanide were measured. A cyanide dose that disrupted this righting reflex for approximately one h with minimal deaths was then selected. Using this paradigm, the current cyanide Antidotes, viz., nitrite plus thiosulfate and hydroxocobalamin, as well as some potential cyanide Antidotes that we developed, were evaluated pre- and post-cyanide. This allowed, for the first time, the assessment of the post-cyanide effectiveness of the current Antidotes against cyanide poisoning in a live animal. In addition, some prototype compounds were found to exhibit antidotal efficacy not only when injected i.p. following cyanide, but also when administered orally 30 min before cyanide. Pre-cyanide oral efficacy suggests that such compounds have the potential of being administered prophylactically before exposure to cyanide. This new test paradigm was found to be a powerful tool for assessing the efficacies of some novel Antidotes against cyanide and should be equally applicable for evaluating putative Antidotes for other neurotoxins.
Steven E. Patterson - One of the best experts on this subject based on the ideXlab platform.
-
simultaneous determination of 3 mercaptopyruvate and cobinamide in plasma by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2016Co-Authors: Michael W Stutelberg, Ilona Petrikovics, Alexandre R. Monteil, Steven E. Patterson, Gerry R Boss, Gary A Rockwood, Joseph K Dzisam, Brian A. LogueAbstract:The current suite of Food and Drug Administration (FDA) approved Antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide Antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide Antidotes. Therefore, a liquid chromatography-tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard ((13)C3-3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN)2). The limits of detection for 3-MP and Cbi were 0.5μM and 0.2μM, respectively. The linear ranges were 2-500μM for 3-MP and 0.5-50μM for Cbi. The accuracy and precision for 3-MP were 100±9% and <8.3% relative standard deviation (RSD), respectively. For Cbi(CN)2, the accuracy was 100±13% and the precision was <9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these Antidotes for treatment of cyanide poisoning.
-
Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3-Mercaptopyruvate for Intramuscular Administration
Journal of medicinal chemistry, 2013Co-Authors: Steven E. Patterson, Alexandre R. Monteil, Jonathan F. Cohen, Daune L. Crankshaw, Robert Vince, Herbert T. NagasawaAbstract:Current cyanide Antidotes are administered by IV infusion, which is suboptimal for mass casualties. Therefore, in a cyanide disaster, intramuscular (IM) injectable Antidotes would be more appropriate. We report the discovery of the highly water-soluble sulfanegen triethanolamine as a promising lead for development as an IM injectable cyanide antidote.
-
A novel paradigm for assessing efficacies of potential Antidotes against neurotoxins in mice.
Toxicology Letters, 2007Co-Authors: Daune L. Crankshaw, Steven E. Patterson, David J. W. Goon, Jacquie E. Briggs, David Delong, Michael A. Kuskowski, Herbert T. NagasawaAbstract:Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD50 for cyanide elicited by the Antidotes. This required the use of high doses of cyanide following pretreatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD50 determinations: we developed a new test paradigm that allowed for maximal survival of cyanide-treated animals with greatly reduced numbers of animals. Symptoms of cyanide toxicity include disruption of neuromuscular coordination, i.e., the righting reflex. Therefore, to establish a dose-response curve, the times required for recovery of this righting reflex with increasing doses of cyanide were measured. A cyanide dose that disrupted this righting reflex for approximately one h with minimal deaths was then selected. Using this paradigm, the current cyanide Antidotes, viz., nitrite plus thiosulfate and hydroxocobalamin, as well as some potential cyanide Antidotes that we developed, were evaluated pre- and post-cyanide. This allowed, for the first time, the assessment of the post-cyanide effectiveness of the current Antidotes against cyanide poisoning in a live animal. In addition, some prototype compounds were found to exhibit antidotal efficacy not only when injected i.p. following cyanide, but also when administered orally 30 min before cyanide. Pre-cyanide oral efficacy suggests that such compounds have the potential of being administered prophylactically before exposure to cyanide. This new test paradigm was found to be a powerful tool for assessing the efficacies of some novel Antidotes against cyanide and should be equally applicable for evaluating putative Antidotes for other neurotoxins.
Daune L. Crankshaw - One of the best experts on this subject based on the ideXlab platform.
-
Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3-Mercaptopyruvate for Intramuscular Administration
Journal of medicinal chemistry, 2013Co-Authors: Steven E. Patterson, Alexandre R. Monteil, Jonathan F. Cohen, Daune L. Crankshaw, Robert Vince, Herbert T. NagasawaAbstract:Current cyanide Antidotes are administered by IV infusion, which is suboptimal for mass casualties. Therefore, in a cyanide disaster, intramuscular (IM) injectable Antidotes would be more appropriate. We report the discovery of the highly water-soluble sulfanegen triethanolamine as a promising lead for development as an IM injectable cyanide antidote.
-
A novel paradigm for assessing efficacies of potential Antidotes against neurotoxins in mice.
Toxicology Letters, 2007Co-Authors: Daune L. Crankshaw, Steven E. Patterson, David J. W. Goon, Jacquie E. Briggs, David Delong, Michael A. Kuskowski, Herbert T. NagasawaAbstract:Historically, antidotal potencies of cyanide antagonists were measured as increases in the experimental LD50 for cyanide elicited by the Antidotes. This required the use of high doses of cyanide following pretreatment with the putative antidote. Since IACUC guidelines at our institutions strongly discourage LD50 determinations: we developed a new test paradigm that allowed for maximal survival of cyanide-treated animals with greatly reduced numbers of animals. Symptoms of cyanide toxicity include disruption of neuromuscular coordination, i.e., the righting reflex. Therefore, to establish a dose-response curve, the times required for recovery of this righting reflex with increasing doses of cyanide were measured. A cyanide dose that disrupted this righting reflex for approximately one h with minimal deaths was then selected. Using this paradigm, the current cyanide Antidotes, viz., nitrite plus thiosulfate and hydroxocobalamin, as well as some potential cyanide Antidotes that we developed, were evaluated pre- and post-cyanide. This allowed, for the first time, the assessment of the post-cyanide effectiveness of the current Antidotes against cyanide poisoning in a live animal. In addition, some prototype compounds were found to exhibit antidotal efficacy not only when injected i.p. following cyanide, but also when administered orally 30 min before cyanide. Pre-cyanide oral efficacy suggests that such compounds have the potential of being administered prophylactically before exposure to cyanide. This new test paradigm was found to be a powerful tool for assessing the efficacies of some novel Antidotes against cyanide and should be equally applicable for evaluating putative Antidotes for other neurotoxins.
Alexandre R. Monteil - One of the best experts on this subject based on the ideXlab platform.
-
simultaneous determination of 3 mercaptopyruvate and cobinamide in plasma by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2016Co-Authors: Michael W Stutelberg, Ilona Petrikovics, Alexandre R. Monteil, Steven E. Patterson, Gerry R Boss, Gary A Rockwood, Joseph K Dzisam, Brian A. LogueAbstract:The current suite of Food and Drug Administration (FDA) approved Antidotes (i.e., sodium nitrite, sodium thiosulfate, and hydroxocobalamin) are effective for treating cyanide poisoning, but individually, each antidote has major limitations (e.g., large effective dosage or delayed onset of action). To mitigate these limitations, next-generation cyanide Antidotes are being investigated, including 3-mercaptopyruvate (3-MP) and cobinamide (Cbi). Analytical methods capable of detecting these therapeutics individually and simultaneously (for combination therapy) are essential for the development of 3-MP and Cbi as potential cyanide Antidotes. Therefore, a liquid chromatography-tandem mass-spectrometry method for the simultaneous analysis of 3-MP and Cbi was developed. Sample preparation of 3-MP consisted of spiking plasma with an internal standard ((13)C3-3-MP), precipitation of plasma proteins, and derivatizing 3-MP with monobromobimane to produce 3-mercaptopyruvate-bimane. Preparation of Cbi involved denaturing plasma proteins with simultaneous addition of excess cyanide to convert each Cbi species to dicyanocobinamide (Cbi(CN)2). The limits of detection for 3-MP and Cbi were 0.5μM and 0.2μM, respectively. The linear ranges were 2-500μM for 3-MP and 0.5-50μM for Cbi. The accuracy and precision for 3-MP were 100±9% and <8.3% relative standard deviation (RSD), respectively. For Cbi(CN)2, the accuracy was 100±13% and the precision was <9.5% RSD. The method presented here was used to determine 3-MP and Cbi from treated animals and may ultimately facilitate FDA approval of these Antidotes for treatment of cyanide poisoning.
-
Cyanide Antidotes for Mass Casualties: Water-Soluble Salts of the Dithiane (Sulfanegen) from 3-Mercaptopyruvate for Intramuscular Administration
Journal of medicinal chemistry, 2013Co-Authors: Steven E. Patterson, Alexandre R. Monteil, Jonathan F. Cohen, Daune L. Crankshaw, Robert Vince, Herbert T. NagasawaAbstract:Current cyanide Antidotes are administered by IV infusion, which is suboptimal for mass casualties. Therefore, in a cyanide disaster, intramuscular (IM) injectable Antidotes would be more appropriate. We report the discovery of the highly water-soluble sulfanegen triethanolamine as a promising lead for development as an IM injectable cyanide antidote.
Alan H. Hall - One of the best experts on this subject based on the ideXlab platform.
-
Which cyanide antidote
Critical reviews in toxicology, 2009Co-Authors: Alan H. Hall, Jane A. SaiersAbstract:Cyanide has several Antidotes, with differing mechanisms of action and diverse toxicological, clinical, and risk-benefit profiles. The international medical community lacks consensus about the antidote or Antidotes with the best risk-benefit ratio. Critical assessment of cyanide Antidotes is needed to aid in therapeutic and administrative decisions that will improve care for victims of cyanide poisoning (particularly poisoning from enclosed-space fire-smoke inhalation), and enhance readiness for cyanide toxic terrorism and other mass-casualty incidents. This paper reviews preclinical and clinical data on available cyanide Antidotes and considers the profiles of these Antidotes relative to properties of a hypothetical ideal cyanide antidote. Each of the Antidotes shows evidence of efficacy in animal studies and clinical experience. The data available to date do not suggest obvious differences in efficacy among Antidotes, with the exception of a slower onset of action of sodium thiosulfate (administered alone) than of the other Antidotes. The potential for serious toxicity limits or prevents the use of the Cyanide Antidote Kit, dicobalt edetate, and 4-dimethylaminophenol in prehospital empiric treatment of suspected cyanide poisoning. Hydroxocobalamin differs from these Antidotes in that it has not been associated with clinically significant toxicity in antidotal doses. Hydroxocobalamin is an antidote that seems to have many of the characteristics of the ideal cyanide antidote: rapid onset of action, neutralizes cyanide without interfering with cellular oxygen use, tolerability and safety profiles conducive to prehospital use, safe for use with smoke-inhalation victims, not harmful when administered to non-poisoned patients, easy to administer.
-
Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning
Annals of emergency medicine, 2006Co-Authors: Alan H. Hall, Richard C. Dart, Gregory M. BogdanAbstract:Cyanide poisoning must be seriously considered in victims of smoke inhalation from enclosed space fires; it is also a credible terrorism threat agent. The treatment of cyanide poisoning is empiric because laboratory confirmation can take hours or days. Empiric treatment requires a safe and effective antidote that can be rapidly administered by either out-of-hospital or emergency department personnel. Among several cyanide Antidotes available, sodium thiosulfate and hydroxocobalamin have been proposed for use in these circumstances. The evidence available to assess either sodium thiosulfate or hydroxocobalamin is incomplete. According to recent safety and efficacy studies in animals and human safety and uncontrolled efficacy studies, hydroxocobalamin seems to be an appropriate antidote for empiric treatment of smoke inhalation and other suspected cyanide poisoning victims in the out-of-hospital setting. Sodium thiosulfate can also be administered in the out-of-hospital setting. The efficacy of sodium thiosulfate is based on individual case studies, and there are contradictory conclusions about efficacy in animal models. The onset of antidotal action of sodium thiosulfate may be too slow for it to be the only cyanide antidote for emergency use. Hydroxocobalamin is being developed for potential introduction in the United States and may represent a new option for emergency personnel in cases of suspected or confirmed cyanide poisoning in the out-of-hospital setting.