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Pharmacology, Toxicology and Environmental Health Commons

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Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Interspecies Differences In Organophosphate Anticholinesterase Inhibition Potency And Reactivation Using Novel Oximes, Katie Elizabeth Strickland May 2023

Interspecies Differences In Organophosphate Anticholinesterase Inhibition Potency And Reactivation Using Novel Oximes, Katie Elizabeth Strickland

Theses and Dissertations

Organophosphates are insecticides which result in acute adverse signs when exposed at toxic doses by animals and lead to death if left untreated. The current treatment for organophosphate toxicity includes atropine and the federally approved oxime 2-PAM. However, 2-PAM is not very effective at crossing the blood brain barrier which results in prolonged inactivation of acetylcholinesterase, which is the primary target of organophosphates, in the brain even after administration. The novel oximes, Oxime 15 and Oxime 20, are able to cross the blood brain barrier and reactivate the inhibited acetylcholinesterase. In this experiment with six animal species frequently used in …


Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo Jan 2016

Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …


Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo Jan 2016

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …