کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4338987 1614896 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro electrophysiological investigations of the acute effects of linezolid and novel oxazolidinones on central nervous system neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
In vitro electrophysiological investigations of the acute effects of linezolid and novel oxazolidinones on central nervous system neurons
چکیده انگلیسی

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 GABAB, dopamine D1-like and α-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.

▶Linezolid, an oxazolidinone depresses NMDA responses only at high concentrations. ▶PH027 and PH084 depress fast synaptic responses at low and high concentrations. ▶PH036 and PH108 have very minimal neuroactivity even at high concentrations. ▶PH036 and PH108 may have least neurotoxic potential.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 180, 28 April 2011, Pages 53–63
نویسندگان
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