Neurophysiological consequences of nitroxide antioxidants

Abstract

Nitroxides are antioxidant compounds that have been shown to provide radioprotection in vivo and in vitro. Radioprotection in vivo is limited by toxicity, which appears to be neurologic in nature. To further evaluate the toxicity of these compounds, three representative nitroxides, Tempol, Tempamine, and Tempo, were examined in slices of guinea pig hippocampus. Each nitroxide increased the population spike and caused potentiation of excitatory postsynaptic potential--spike coupling. Repetitive activity and epileptiform activity were observed at the highest concentrations of Tempo and Tempamine. Tempol was the least toxic compound in this system, followed by Tempamine and Tempo. Additional studies are necessary to further define the effects of nitroxides on the central nervous system and to develop strategies to mitigate these effects.

Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides

“…Nitroxides added to slices of guinea pig hippocampus in the concentration range of 1 to 5 mM increased the neural excitability, but tempol was less toxic than tempo or tempamine (Hahn et al, 1995). …”

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“…KEYWORDS: brain edema n contrast-enhanced ultrasound n focused ultrasound n intracerebral hemorrhage n microbubbles n nitroxide-radical containing nanoparticle n oxidative stress n reactive oxygen species n redox-polymer drug n self-assembling polymer micelle such as nitroxide radical compounds, have been employed for suppression of such oxidative compounds. The nitroxide radical compound 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) is one of the strongest antioxidants that catalytically scavenges ROS [17,18]. Under in vivo conditions, however, these low molecular weight nitroxide compounds have several problems, including nonspecific dispersion in normal tissues, preferential renal clearance and rapid reduction to the corresponding hydroxylamine form.…”

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“…For example, high doses of the parent spin trap compound PBN cause impaired respiration, abnormal blood chemistry, seizures and tissue damage [166]. The broad spectrum of potential side effects may be explained by the pharmacokinetic profile of the drug, especially its ability to distribute throughout the body after peripheral administration and its slow clearance rate [167].…”