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 | |
| Publication status | Published - 2012 Nov 1 |
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Keywords
- c-Fos
- Formalin test
- Inflammatory pain
- Neuropathic pain
- Nociception
- Sodium channel
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Pharmacology
- Toxicology
- Behavioral Neuroscience
- Biological Psychiatry
Cite this
HYP-1, a novel diamide compound, relieves inflammatory and neuropathic pain in rats. / Kam, Yoo Lim; Back, Seung Keun; Kang, Bohee; Kim, Young Yun; Kim, Hwa Jung; Rhim, Hyewhon; Nah, Seung Yeol; Chung, Jun Mo; Kim, Dong Hyun; Choi, Jin Sung; Na, Heung Sik; Choo, Hea Young Park.
In: Pharmacology Biochemistry and Behavior, Vol. 103, No. 1, 01.11.2012, p. 33-42.Research output: Contribution to journal › Article
}
TY - JOUR
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
PY - 2012/11/1
Y1 - 2012/11/1
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.
AB - 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.
KW - c-Fos
KW - Formalin test
KW - Inflammatory pain
KW - Neuropathic pain
KW - Nociception
KW - Sodium channel
UR - http://www.scopus.com/inward/record.url?scp=84865311962&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865311962&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2012.07.010
DO - 10.1016/j.pbb.2012.07.010
M3 - Article
VL - 103
SP - 33
EP - 42
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 1
ER -