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.
authors.affiliation: School of Pharmacy, Ewha Womans University, Seoul 120–750, Republic of Korea.
authors.forename: Yoo Lim
authors.initials: YL
authors.lastname: Kam
authors.forename: Seung Keun
authors.initials: SK
authors.lastname: Back
authors.forename: Bohee
authors.initials: B
authors.lastname: Kang
authors.forename: Young-Yun
authors.initials: YY
authors.lastname: Kim
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
authors.forename: Jun-mo
authors.initials: JM
authors.lastname: Chung
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jin-Sung
authors.initials: JS
authors.lastname: Choi
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Na
authors.forename: Hea-Young Park
authors.initials: HY
authors.lastname: Choo
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D018408:Patch-Clamp Techniques; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D061567:Voltage-Gated Sodium Channel Blockers / Q000138:chemical synthesis / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: C579845:2-(2-(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)-2-oxoethylamino)-N-(3,4,5-trimethoxybenzyl)acetamide; D000081:Acetamides; D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016760:Proto-Oncogene Proteins c-fos; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels