HYP-1, a novel diamide compound, relieves inflammatory and neuropathic pain in rats

Yoo Lim Kam, Seung Keun Back, Bohee Kang, Young Yun Kim, Hwa Jung Kim, Hyewhon Rhim, Seung Yeol Nah, Jun Mo Chung, Dong Hyun Kim, Jin Sung Choi, Heung Sik Na, Hea Young Park Choo

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3 Scopus citations


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.

Original languageEnglish
Pages (from-to)33-42
Number of pages10
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Nov 2012

Bibliographical note

Funding Information:
We thank SK Chemical for financial support on MDS Pharma Services tests. This study was supported in part by the Korea Research Foundation (Grant KRF-2005-041-E20291 ), a special research grant from EWU (JMC), a grant ( 2011 K000275 ) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea and a Korea University grant. Also this work was supported by the research fund, 2012 of The Catholic University of Korea .


  • Formalin test
  • Inflammatory pain
  • Neuropathic pain
  • Nociception
  • Sodium channel
  • c-Fos


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