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

doi:10.1016/j.pbb.2012.07.010

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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 language	English
Pages (from-to)	33-42
Number of pages	10
Journal	Pharmacology Biochemistry and Behavior
Volume	103
Issue number	1
DOIs	https://doi.org/10.1016/j.pbb.2012.07.010
State	Published - 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 .

Keywords

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

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10.1016/j.pbb.2012.07.010

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

abstract = "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.",

keywords = "Formalin test, Inflammatory pain, Neuropathic pain, Nociception, Sodium channel, c-Fos",

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

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 .",

year = "2012",

month = nov,

doi = "10.1016/j.pbb.2012.07.010",

language = "English",

volume = "103",

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T1 - HYP-1, a novel diamide compound, relieves inflammatory and neuropathic pain in rats

AU - Kam, Yoo Lim

AU - Back, Seung Keun

AU - Kang, Bohee

AU - Kim, Young Yun

AU - Kim, Hwa Jung

AU - Rhim, Hyewhon

AU - Nah, Seung Yeol

AU - Chung, Jun Mo

AU - Kim, Dong Hyun

AU - Choi, Jin Sung

AU - Na, Heung Sik

AU - Choo, Hea Young Park

N1 - 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 .

PY - 2012/11

Y1 - 2012/11

N2 - 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.

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KW - Inflammatory pain

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

Abstract

Bibliographical note

Keywords

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