Intramuscular atenolol and levetiracetam reduce mortality in a rat model of paraoxon-induced status epilepticus.
beta-blocker
mortality
paraoxon
pharmacokinetics
safety
status epilepticus
Journal
Annals of the New York Academy of Sciences
ISSN: 1749-6632
Titre abrégé: Ann N Y Acad Sci
Pays: United States
ID NLM: 7506858
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
24
04
2020
revised:
21
08
2020
accepted:
01
09
2020
pubmed:
23
9
2020
medline:
31
12
2020
entrez:
22
9
2020
Statut:
ppublish
Résumé
Organophosphorus (OP) compounds are chemical threat agents and are irreversible inhibitors of the enzyme acetylcholinesterase that lead to a hypercholinergic response that could include status epilepticus (SE). SE particularly targets the heart and brain and despite existing therapies, it is still associated with significant mortality and morbidity. Here, we investigated the effect of intramuscular (i.m.) adjunct therapy consisting of atenolol (AT) and levetiracetam (LV) when administered after paraoxon (POX)-induced SE. The combination therapy was administered twice daily for 2, 7, or 14 days. POX exposure in rats produced rapid SE onset that was treated with atropine, pralidoxime chloride, and midazolam. Here, AT + LV therapy produced significant reductions in POX SE mortality assessed at 30 days post-SE. AT + LV therapy exhibited muscle pathology inflammation scores that were not significantly different from saline-treated controls. Pharmacokinetic analyses revealed that the i.m. route achieved faster and stabler plasma therapeutic levels for both AT and LV under OP SE conditions compared with oral administrations. Our data provide evidence of the safety and efficacy of i.m. AT + LV therapy for reducing mortality following POX SE.
Identifiants
pubmed: 32961584
doi: 10.1111/nyas.14500
pmc: PMC7708441
mid: NIHMS1645945
doi:
Substances chimiques
Levetiracetam
44YRR34555
Atenolol
50VV3VW0TI
Paraoxon
Q9CX8P80JW
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
219-232Subventions
Organisme : NINDS NIH HHS
ID : U01 NS105058
Pays : United States
Informations de copyright
© 2020 New York Academy of Sciences.
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