HYP-1, a novel diamide compound, relieves inflammatory and neuropathic pain in rats
| Autor: | Jin-Sung Choi, Heung Sik Na, Yoo Lim Kam, Hea Young Park Choo, Dong Hyun Kim, Seung Keun Back, Hyewhon Rhim, Bohee Kang, Seung Yeol Nah, Jun Mo Chung, Young Yun Kim, Hwa Jung Kim |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Patch-Clamp Techniques Sensory Receptor Cells Clinical Biochemistry Analgesic Voltage-Gated Sodium Channels Pharmacology Toxicology Biochemistry Rats Sprague-Dawley Behavioral Neuroscience Dorsal root ganglion Ganglia Spinal Acetamides medicine Animals Humans Biological Psychiatry Pain Measurement Inflammation Voltage-Gated Sodium Channel Blockers business.industry Anti-Inflammatory Agents Non-Steroidal Analgesics Non-Narcotic Nerve injury Sensory neuron Rats HEK293 Cells medicine.anatomical_structure Allodynia Nociception Hyperalgesia Anesthesia Neuropathic pain Neuralgia medicine.symptom business Proto-Oncogene Proteins c-fos |
| Zdroj: | Pharmacology Biochemistry and Behavior. 103:33-42 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2012.07.010 |
| Popis: | In the present study, we investigated whether a novel compound, 2-(2-(4-((4-chlorophenyl)(phenyl)methyl) piperazin-1-yl)-2-oxoethylamino)-N-(3,4,5-trimethoxybenzyl)acetamide (HYP-1), is capable of binding to voltage-gated sodium channels (VGSCs) and evaluated both its inhibitory effect on Na+ currents of the rat dorsal root ganglia (DRG) sensory neuron and its in vivo analgesic activity using rat models of inflammatory and neuropathic pain. HYP-1 showed not only high affinity for rat sodium channel (site 2), but also potent inhibitory activity against the TTX-R Na+ currents of the rat DRG sensory neuron. HYP-1 co-injected with formalin (5%, 50 μl) under the plantar surface of rat hind paw dose-dependently reduced spontaneous pain behaviors during both the early and late phases. This result was confirmed by c-Fos immunofluorescence in the L4-5 spinal segments. A large number of c-Fos-positive neurons were observed in rat injected with a mixture of formalin and vehicle, but not in rat treated with a mixture of formalin and HYP-1. In addition, the effectiveness of HYP-1 (6 and 60 mg/kg, i.p.) in suppression of neuropathic pain, such as mechanical, cold and warm allodynia, induced by rat tail nerve injury was investigated. HYP-1 showed limited selectivity over hERG, N-type and T-type channels.Our present results indicate that HYP-1, as a VGSC blocker, has potential analgesic activities against nociceptive, inflammatory and neuropathic pain. |
| Databáze: | OpenAIRE |
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