Linked Life Data

21296129

Source:http://linkedlifedata.com/resource/pubmed/id/21296129

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2011-4-4
pubmed:abstractText
Oxazolidinones are a novel class of antibacterial agents with demonstrated activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and enterococci. Prolonged clinical use of linezolid, the prototypical oxazolidinone, results in peripheral, central and optic neuropathies. The cellular mechanism by which it may alter neuronal function to produce these effects is not known. This study examined the in vitro effects of clinically relevant concentrations of linezolid and four selected potent antibacterial oxazolidinones on neuronal responses to determine if they are neuroactive and their possible neurotoxic mechanism(s). Using in vitro slice preparations of the rat nucleus accumbens (NAc) and hippocampus, we examined the effects of linezolid and the potent antibacterial triazolyl oxazolidinones, PH027, PH036, PH084 and PH108 on synaptic transmission and neuronal excitability recorded in voltage or current clamp mode. PH027 and PH084 generally depressed all excitatory and inhibitory postsynaptic currents. Linezolid, at the highest concentration tested, depressed NMDA receptor-mediated currents while PH036 and PH108 had no significant effect on any of these responses. The synaptic depression by PH084 was without effect on the resting membrane conductance at resting or relatively hyperpolarized voltage and could be blocked by GABA(B), dopamine D1-like and ?-adrenergic receptor antagonists but not by an adenosine A1 receptor antagonist. Finally, PH084 decreased action potential firing frequency of NAc and hippocampal cells elicited at depolarized potentials. Our data indicate that, while oxazolidinones containing both the morpholine and triazole functional groups, as in PH027 and PH084, have neuroactivity, those containing morpholine and acetamide (linezolid) or piperazine and triazolyl (PH036 and PH108) functional groups have minimal acute neuroactivity and therefore may be safer antibacterial agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1873-7544
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-63
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
In vitro electrophysiological investigations of the acute effects of linezolid and novel oxazolidinones on central nervous system neurons.
pubmed:affiliation
Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. kombian@hsc.edu.kw
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't