Effects of fosphenytoin on nerve agent-induced status epilepticus.

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  • Additional Information
    • Source:
      Publisher: Taylor & Francis Group Country of Publication: United States NLM ID: 7801723 Publication Model: Print Cited Medium: Print ISSN: 0148-0545 (Print) Linking ISSN: 01480545 NLM ISO Abbreviation: Drug Chem Toxicol Subsets: MEDLINE
    • Publication Information:
      Publication: [Philadelphia, PA] : Taylor & Francis Group
      Original Publication: New York, Dekker.
    • Subject Terms:
      Anticonvulsants/*therapeutic use ; Chemical Warfare Agents/*toxicity ; Phenytoin/*analogs & derivatives ; Phenytoin/*therapeutic use ; Soman/*antagonists & inhibitors ; Soman/*toxicity ; Status Epilepticus/*drug therapy; Animals ; Anticonvulsants/administration & dosage ; Atropine/pharmacology ; Diazepam/pharmacology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Electroencephalography/drug effects ; Guinea Pigs ; Injections, Intraperitoneal ; Male ; Phenytoin/administration & dosage ; Pralidoxime Compounds/pharmacology ; Pyridostigmine Bromide/pharmacology ; Status Epilepticus/chemically induced ; Status Epilepticus/physiopathology
    • Abstract:
      This study evaluated the effectiveness of fosphenytoin as a single or adjunctive anticonvulsant treatment for nerve agent-induced status epilepticus. Guinea pigs, implanted with cortical electroencephalographic (EEG) recording electrodes, were pretreated with pyridostigmine bromide (0.026 mg/kg, intramuscular (i.m.)) 30 min before challenge with 56 micrograms/kg, subcutaneous (s.c.), (2 x LD50) of the nerve agent soman. One min after soman, the animals were treated (i.m.) with 2 mg/kg atropine sulfate admixed with 25 mg/kg of the oxime 2-pralidoxime chloride, and the EEG was observed for seizure onset. When administered (intraperitoneal, i.p.) therapeutically 5 min after seizure onset, only the highest fosphenytoin dose (180 mg/kg) was capable of terminating seizure activity in 50% of the animals tested (3 of 6). When fosphenytoin (18-180 mg/kg) was administered as a pretreatment, i.p., 30 min before soman challenge, seizures were blocked or terminated in a dose-dependent fashion (ED50 = 61.8 mg/kg; 40.5-94.7 mg/kg = 95% confidence limits). Combinations of diazepam and fosphenytoin were also tested for effectiveness. No dose of fosphenytoin (18-56 mg/kg), given in conjunction with a fixed dose of diazepam (4.8 mg/kg, i.m.) 5 min after seizure onset, enhanced the anticonvulsant effect of diazepam. When fosphenytoin (18 or 32 mg/kg, i.p.) was given as a pretreatment and diazepam was given 5 min after seizure onset, the 32 mg/kg dose of fosphenytoin significantly reduced the time for seizure control. These studies show that fosphenytoin, either alone or in combination with diazepam, has little or no therapeutic anticonvulsant effectiveness for nerve agent-induced status epilepticus.
    • Accession Number:
      0 (Anticonvulsants)
      0 (Chemical Warfare Agents)
      0 (Pralidoxime Compounds)
      6158TKW0C5 (Phenytoin)
      7C0697DR9I (Atropine)
      96-64-0 (Soman)
      B4SF212641 (fosphenytoin)
      KVI301NA53 (Pyridostigmine Bromide)
      P7MU9UTP52 (pralidoxime)
      Q3JTX2Q7TU (Diazepam)
    • Publication Date:
      Date Created: 20040325 Date Completed: 20041007 Latest Revision: 20191108
    • Publication Date:
      20240829
    • Accession Number:
      10.1081/dct-120027895
    • Accession Number:
      15038246