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

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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 ITX-R Na+ currents of the rat DRG sensory neuron. HYP-1 co-injected with formalin (5%, 50 mu l) 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. (c) 2012 Elsevier Inc. All rights reserved.
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Issue Date
2012-11
Language
English
Article Type
Article
Keywords

SODIUM-CHANNEL BLOCKERS; DORSAL-ROOT GANGLION; SENSORY NEURONS; SUBCUTANEOUS FORMALIN; NERVE INJURY; BMK IT2; TACTILE ALLODYNIA; NA+ CHANNELS; DRG NEURONS; 3 SUBTYPES

Citation

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, v.103, no.1, pp.33 - 42

ISSN
0091-3057
DOI
10.1016/j.pbb.2012.07.010
URI
http://hdl.handle.net/10203/102961
Appears in Collection
RIMS Journal Papers
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