Anticonvulsants for poisoning by the organophosphorus compound soman: Pharmacological mechanisms

Shih, Tsung‐Ming; Koviak, Thomas A.; Capacio, Benedict R.

doi:10.1016/s0149-7634(05)80028-4

Cited by 179 publications

(108 citation statements)

References 91 publications

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“…The differences in potency between these three anticholinergics across agents is the same as first reported against soman Shih et al, 1991). When compared with any given agent, trihexyphenidyl is more potent than biperiden, which, in turn, is more potent than atropine, while biperiden controlled seizures significantly more rapidly than trihexyphenidyl.…”

Section: Discussionsupporting

confidence: 59%

Control of Nerve Agent-Induced Seizures is Critical for Neuroprotection and Survival

Shih¹,

Duniho²,

McDonough³

2002

103

196

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Section: Discussionsupporting

confidence: 59%

Control of Nerve Agent-Induced Seizures is Critical for Neuroprotection and Survival

Shih¹,

Duniho²,

McDonough³

2002

103

196

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“…After carbamate pretreatment, a multidrug complex including a cholinolytic agent (generaly atropin), an oxime reactivator and an anticonvulsant is necessary for posttreatment of patients. Diazepam has been generally used as anticonvulsant together with atropin, but its injectable form has associated with its drawback such as abuse liability, nonaqueos formulation and delibilitating side effects which make it less preferable for military personnel in the battle field (45). It is proposed that benactyzine has more efficiency in preventing somaninduced convulsions in the tested animals.…”

Section: Anticonvulsant Drugsmentioning

confidence: 99%

Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination

Jebali¹,

Khedher²,

Sabbagh³

et al. 2013

RGCI

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Butyrylcholinesterase is involved three different enzymatic activities in its structure like its sister enzyme, acetylcholinesterase: esterase, aryl acylamidase and peptidase (or protease). Whereas the clear role of acetylcholinesterase in cholinergic neurotransmission is well defined, the real physiological function of butyrylcholinesterase is still unknown. Both enzymes have similar molecular forms with different tissue distribution. Esteratic activity of butyrylcholinesterase becomes more important in scavenging of organophosphate and carbamate inhibitors before they reach to acetylcholinesterase; in regulating cholinergic transmission in the absence of acetylcholinesterase and in inactivation of some drugs such as cocaine aspirin, amitriptyline or in activation of others such as bambuterol, heroin. It is suggested that aryl acylamidase activity plays a role in crosstalking between seratonergic and cholinergic neurotransmission systems. In addition, peptidase activity of butyrylcholinesterase has a function in the development and progression of Alzheimer disease due to cause the production of β-amyloid protein and to help its diffusion to β-amyloid plaques.

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“…Data extrapolated from pharmacokinetic studies in soman-exposed guinea pigs t suggest that im administration of 3 autoinjectors of diazepam (30 mg) to a 70-75 kg human (0.4-0.43 mg/kg) may result in less than optimal plasma levels and latency to drug action in an emergency military treatment setting . Midazolam has been shown to be effective for treating seizure/convulsions associated with exposure to multiple lethal doses of OP cholinesterase inhibitors (Anderson et al, 1997;Shih et al, 1991). Additionally, in guinea pigs with somaninduced seizure activity, midazolam was shown to act more quickly and at much lower doses than diazepam following im administration (McDonough et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Studies of Intramuscular Midazolam in Guinea Pigs Challenged with Soman

Capacio

Byers

Merk

et al. 2004

Drug and Chemical Toxicology

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Studies have demonstrated that benzodiazepine compounds are effective at antagonizing seizure activity produced by the organophosphate (OP) cholinesterase inhibitor soman. In this present study we have investigated the pharmacokinetics of midazolam and its associated effects on electroencephalographic (EEG) activity following intramuscular (im) injection to soman-exposed guinea pigs (Crl:(HA)BR).Prior to experiments, the animals were surgically implanted with EEG leads to monitor seizure activity. For the study, animals were administered the following pretreatment/OP/treatment regimen. Pyridostigmine bromide (0.026 mg/kg, im) was given 30 min prior to soman (56 gtg/kg, 2 x LDso; subcutaneously, sc), followed in one minute by atropine sulfate (2 mg/kg, im) and pralidoxime chloride (25 mg/kg, im). All animals receiving this regimen developed seizure activity. Midazolam 0.8 mg/kg, im, was administered 5 min after onset of seizure activity. Based on EEG data, animals were categorized as either seizure-terminated or seizure not-terminated at 30 min following anticonvulsant administration. Serial blood samples were collected *In conducting the research described in this report, the investigators complied with the regulations and standards of the Animal Welfare Act and adhered to the principles of the Guide for the Care and Use of Laboratory Animals (NRC 1996 for the plasma midazolam analysis; the assay was accomplished with a gas chromatograph/mass spectrometer. The mean time to seizure termination was 8.8 ± 1.6 min. The mean time-plasma concentration data were fit to standard pharmacokinetic models. The following parameter estimates were determined from the model-fit for seizure terminated and not-terminated animals respectively: apparent volumes of distribution (Vd) were 1.4 and 1.7 1/kg; area under the time-concentration curves (AUC), 15,990 and 15,120 ng . minrml; times to maximal plasma concentration (Tma,), 1.66 and 2.91 min and maximal plasma concentrations (Cmnx) 535.1 and 436.6 ng/ml. These data indicate that im injection of midazolam is effective at terminating ongoing soman-induced seizure activity. Additionally, the relatively short Tmax and latency to seizure termination demonstrate the rapidity of drug absorption and action respectively.

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Anticonvulsants for poisoning by the organophosphorus compound soman: Pharmacological mechanisms

Cited by 179 publications

References 91 publications

Control of Nerve Agent-Induced Seizures is Critical for Neuroprotection and Survival

Control of Nerve Agent-Induced Seizures is Critical for Neuroprotection and Survival

Cholinesterase activity as biomarker of neurotoxicity: utility in the assessment of aquatic environment contamination

Pharmacokinetic Studies of Intramuscular Midazolam in Guinea Pigs Challenged with Soman

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