Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Feb 2017
HYP-17, a novel voltage-gated sodium channel blocker, relieves inflammatory and neuropathic pain in rats.
Clinical and experimental studies suggest that voltage-gated sodium channels (VGSCs) play a key role in the pathogenesis of neuropathic pain and that blocking agents against these channels can be potentially therapeutic. In the current study, we investigated whether a novel compound, (-)-2-Amino-1-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-propan-1-one(HYP-17), binds to VGSCs and evaluated its inhibitory effect on Na+ currents of the rat dorsal root ganglia (DRG) sensory neurons and its analgesic effect on inflammatory and neuropathic pain. HYP-17 (10μM) reduced both the tetrodotoxin-sensitive (TTX-S) and the TTX-resistant (TTX-R) currents in DRG sensory neurons. ⋯ Electrophysiological study showed that HYP-17 significantly attenuated the hyper-responsiveness of lumbar dorsal horn neurons. In addition, HYP-17 significantly reduced the levels of pp38MAPK and p-JNK in microglia and astrocytes, respectively, in the L4-L5 spinal dorsal horn. Therefore, our results indicate that HYP-17 has potential analgesic activities against nociceptive, inflammatory and neuropathic pain.
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Pharmacol. Biochem. Behav. · Feb 2017
WY-14643, a selective agonist of peroxisome proliferator-activated receptor-α, ameliorates lipopolysaccharide-induced depressive-like behaviors by preventing neuroinflammation and oxido-nitrosative stress in mice.
Depression is a common disease that afflicts one in six people at some points in life. Numerous hypotheses have been raised in past years, but the exact mechanism that can be used to explain the development of depression remains obscure. Recently, more and more attentions are being focused on neuroinflammation and oxidative stress in depression. ⋯ Further analysis showed that WY-14643 pretreatment not only inhibited the production of pro-inflammatory cytokines induced by LPS, such as interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but also prevented the LPS-induced enhancement of oxidative and nitrosative stress in the hippocampus and prefrontal cortex. In addition, the LPS-induced decreases in hippocampal and prefrontal cortical brain-derived neurotrophic factor (BDNF) levels were reversed by WY-14643 pretreatment. Taken together, our data provide further evidence to show that WY-14643 could be an agent that can be used to treat depression, and inhibition of neuroinflammation and oxido-nitrosative stress may be the potential mechanism for the antidepressive effect of WY-14643.