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Valnoctamide and sec-butyl-propylacetamide SPD for acute seizures and status epilepticus

Shekh-Ahmad, T; Hen, N; McDonough, JH; Yagen, B; Bialer, M; (2013) Valnoctamide and sec-butyl-propylacetamide SPD for acute seizures and status epilepticus. Epilepsia , 54 pp. 99-102. 10.1111/epi.12290. Green open access

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Abstract

sec-Butyl-propylacetamide (SPD) is a one-carbon homologue of valnoctamide (VCD), a chiral constitutional isomer of valproic acid’s (VPA) corresponding amide valpromide. VCD has a potential in epilepsy including status epilepticus (SE) and neuropathic pain, and is currently being developed for the treatment of bipolar disorder. Both VCD and SPD possess two stereogenic carbons in their chemical structure. SPD possess a unique and broad-spectrum antiseizure profile superior to that of VPA and better than that of VCD. In addition SPD blocked behavioral- and electrographic-SE induced by pilocarpine and soman (organophosphate nerve gas) and afforded in vivo neuroprotection that was associated with cognitive sparing. VCD has similar activity as SPD in the pilocarpine-induced-SE although at higher doses. The activity of SPD and VCD against SE is superior to that of diazepam in terms of rapid onset, potency and ability to block SE when given 20 to 60 min after seizure onset. When administered 20 and 40min after SE onset, SPD (100–174mg/kg) produced long-lasting efficacy (e.g., 4–8hr) against soman-induced convulsive- and electrographic-SE in both rats and guinea pigs. SPD activity in the pilocarpine-and soman-induced SE models when administered 20 to 60 min after seizure onset differentiates SPD from benzodiazepines and all other AEDs.

Type: Article
Title: Valnoctamide and sec-butyl-propylacetamide SPD for acute seizures and status epilepticus
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/epi.12290
Publisher version: https://doi.org/10.1111/epi.12290
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: sec-Propylbutyl-acetamide, valnoctamide, soman-induced status epielpticus, benzodiazepine-resistant status epilepticus
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10075727
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