Cholinergic systems influence local cerebral glucose use in specific anatomical areas: Diisopropyl phosphorofluoridate versus soman

Churchill, Lynn; Pazdernik, Thomas L.; Cross, Robert S.; Giesler, M.; Nelson, Stanley R.; Samson, Frederick E.

doi:10.1016/0306-4522(87)90023-6

Cited by 19 publications

(11 citation statements)

References 29 publications

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“…The authors (Finkelstein et al, 1988) concluded that a detailed knowledge of the brain regions affected by OP poisoning may explain some of the clinical manifestations of poisonings by these compounds. These results were in partial agreement with findings obtained in experimental animal studies (Churchill et al, , 1987(Churchill et al, ). 1988a.…”

Section: Choline Uptake Is a Target For The Effects Of Organophosphorsupporting

confidence: 95%

“…Churchill et al (1987) gave s.c. injections of soman or DFP to SD rats. Soman rapidly induced tonic-clonic convulsions, whereas DFP only occasionally induced transient seizurelike activity.…”

Section: Effects Of Brain Metabolismmentioning

confidence: 98%

“…In fact, some of the dramatic differences between OP compounds that cause some of their serious toxic effects such as convulsions are related to their affinities for AChE (see Churchill et al, 1987; …”

Section: Acetylcholinesterasementioning

confidence: 99%

“…An example of the compounds in this group is the drug ecothiopate. Category II includes the warfare nerve agents soman and sarin, as well as diisopropyl phosphofluoridate (DFP) (see Churchill et al, 1987;Savolainen et al, 1988a, b), where the leaving group is fluorine. In category III, the leaving group is cyanide, cyanate, thio- cyanate, or a halogen other than fluorine.…”

Section: Chemistry Of Organophosphorus Compoundsmentioning

confidence: 99%

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Understanding the Toxic Actions of Organophosphates

Savolainen

2001

Handbook of Pesticide Toxicology

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Section: Choline Uptake Is a Target For The Effects Of Organophosphorsupporting

confidence: 95%

Section: Effects Of Brain Metabolismmentioning

confidence: 98%

Section: Acetylcholinesterasementioning

confidence: 99%

Section: Chemistry Of Organophosphorus Compoundsmentioning

confidence: 99%

See 2 more Smart Citations

Understanding the Toxic Actions of Organophosphates

Savolainen

2001

Handbook of Pesticide Toxicology

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“…Indeed, using OP animal models as a surrogate for NA exposure would be ideal, since OPs are safer for researchers to handle and more readily available. However, readers should be cautioned that, despite sharing a primary mechanism of toxicity, different organophosphorus agents may be more or less likely to induce SE, respond to different countermeasures, or increase metabolic activity in key brain regions . The reasons for differences as well as similarities between how OPs and NAs act in different animal models still need to be thoroughly explored through basic research to accurately interpret any test results in a given model.…”

Section: Pesticide Modelsmentioning

confidence: 99%

Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides

McCarren

McDonough

2016

Annals of the New York Academy of Sciences

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Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit.

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Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins

et al. 2001

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Soman, a potent acetylcholinesterase inhibitor, induces status epilepticus in rats followed by conspicuous neuropathology, most prominent in piriform cortex and the CA3 region of the hippocampus. Cholinergic seizures originate in striatal-nigral pathways and with fast-acting agents (soman) rapidly spread to limbic related areas and finally culminate in a full-blown status epilepticus. This leads to neurochemical changes, some of which may be neuroprotective whereas others may cause brain damage. Pretreatment with lithium sensitizes the brain to cholinergic seizures. Likewise, other agents that increase limbic hyperactivity may sensitize the brain to cholinergic agents. The hyperactivity associated with the seizure state leads to an increase in intracellular calcium, cellular edema and metal delocalization producing an oxidative stress. These changes induce the synthesis of stress-related proteins such as heat shock proteins, metallothioneins and heme oxygenases. We show that soman-induced seizures cause a depletion in tissue glutathione and an increase in tissue 'catalytic' iron, metallothioneins and heme oxygenase-1. The oxidative stress induces the synthesis of stress-related proteins, which are indicators of 'stress' and possibly provide neuroprotection. These findings suggest that delocalization of iron may catalyze Fenton-like reactions, causing progressive cellular damage via free radical products. Published in

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Cholinergic systems influence local cerebral glucose use in specific anatomical areas: Diisopropyl phosphorofluoridate versus soman

Cited by 19 publications

References 29 publications

Understanding the Toxic Actions of Organophosphates

Understanding the Toxic Actions of Organophosphates

Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides

Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins

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