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Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity

OBJECTIVE: To test the hypothesis that a triazolyloxazolidinone (PH084) has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus. MATERIALS AND METHODS: Whole-cell synaptic currents, action potentials and extracellular population spikes (PS) were recorde...

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Autores principales: Kombian, Samuel B., Phillips, Oludotun A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586748/
https://www.ncbi.nlm.nih.gov/pubmed/23257573
http://dx.doi.org/10.1159/000346005
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author Kombian, Samuel B.
Phillips, Oludotun A.
author_facet Kombian, Samuel B.
Phillips, Oludotun A.
author_sort Kombian, Samuel B.
collection PubMed
description OBJECTIVE: To test the hypothesis that a triazolyloxazolidinone (PH084) has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus. MATERIALS AND METHODS: Whole-cell synaptic currents, action potentials and extracellular population spikes (PS) were recorded in the cell body area of rat hippocampal CA1 region in acutely prepared slices. Chemical [picrotoxin (100 µM) and zero magnesium] and electrical seizures were induced and the effect of PH084 (10 µM) was tested on cellular responses, multiple spikes and spontaneous bursting frequencies. RESULTS: PH084 depressed evoked excitatory postsynaptic currents, action potential firing frequency and PS amplitude. All of these responses did not recover to baseline after 15–20 min washout of PH084. Perfusion with zero magnesium ion (Mg(2s+))-containing buffer converted a single PS to multiple PS (mPS) accompanied by spontaneous burst. PH084 suppressed the mPS and the spontaneous burst frequency and it also suppressed the picrotoxin-induced mPS number. However, it did not affect the frequency of stimulus train-induced after discharge or bursts. Furthermore, 8–10 min pretreatment with PH084 did not affect the ability of zero Mg(2s+) buffer, picrotoxin or stimulus train to induce epileptiform activity. CONCLUSIONS: Thus, while PH084 may have potential for anticonvulsant activity against chemically induced seizures, it has little or no potential against electrically induced seizures or in preventing epileptiform discharge.
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spelling pubmed-55867482017-11-01 Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity Kombian, Samuel B. Phillips, Oludotun A. Med Princ Pract Original Paper OBJECTIVE: To test the hypothesis that a triazolyloxazolidinone (PH084) has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus. MATERIALS AND METHODS: Whole-cell synaptic currents, action potentials and extracellular population spikes (PS) were recorded in the cell body area of rat hippocampal CA1 region in acutely prepared slices. Chemical [picrotoxin (100 µM) and zero magnesium] and electrical seizures were induced and the effect of PH084 (10 µM) was tested on cellular responses, multiple spikes and spontaneous bursting frequencies. RESULTS: PH084 depressed evoked excitatory postsynaptic currents, action potential firing frequency and PS amplitude. All of these responses did not recover to baseline after 15–20 min washout of PH084. Perfusion with zero magnesium ion (Mg(2s+))-containing buffer converted a single PS to multiple PS (mPS) accompanied by spontaneous burst. PH084 suppressed the mPS and the spontaneous burst frequency and it also suppressed the picrotoxin-induced mPS number. However, it did not affect the frequency of stimulus train-induced after discharge or bursts. Furthermore, 8–10 min pretreatment with PH084 did not affect the ability of zero Mg(2s+) buffer, picrotoxin or stimulus train to induce epileptiform activity. CONCLUSIONS: Thus, while PH084 may have potential for anticonvulsant activity against chemically induced seizures, it has little or no potential against electrically induced seizures or in preventing epileptiform discharge. S. Karger AG 2013-06 2012-12-21 /pmc/articles/PMC5586748/ /pubmed/23257573 http://dx.doi.org/10.1159/000346005 Text en Copyright © 2012 by S. Karger AG, Basel http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
spellingShingle Original Paper
Kombian, Samuel B.
Phillips, Oludotun A.
Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity
title Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity
title_full Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity
title_fullStr Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity
title_full_unstemmed Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity
title_short Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity
title_sort novel actions of oxazolidinones: in vitro screening of a triazolyloxazolidinone for anticonvulsant activity
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586748/
https://www.ncbi.nlm.nih.gov/pubmed/23257573
http://dx.doi.org/10.1159/000346005
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