Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain

被引:50
作者
Stöhr, T
Krause, E
Selve, N
机构
[1] Schwarz BioSci GmbH, Dept Pharmacol Toxicol, D-40789 Monheim, Germany
[2] Univ Halle Wittenberg, Inst Pharmceut Biol & Pharmacol, D-06120 Halle, Germany
关键词
inflammatory pain; antiepileptic drug; lacosamide; arthritis; formalin test; carrageenan test;
D O I
10.1016/j.ejpain.2005.04.002
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Lacosamide is a functionalized amino acid which was initially synthesized as an antiepileptic drug. In addition to its broad antiseizure activity, lacosamide wits shown to display efficacy in animal models for neuropathic pain and is Currently in phase III clinical development for the treatment of epilepsy and neuropathic pain. In order to further profile its antinociceptive properties, the effects of lacosamide on inflammatory pain in the formalin test, the carrageenan model and the adjuvant-induced arthritis model were investigated. For the formalin test, mice received an intraplantar injection of formalin and the subsequent licking response was measured over 45 min. Lacosamide was administered 30 min before formalin. For the carrageenan model, mechanical and thermal hyperalgesia were assessed 3 h following an intraplantar injection of carrageenan. Lacosamide was administered to rats 30 min before pain threshold measurements. For the adjuvant-induced arthritis test rats received intraplantar injections of Freund's complete adjuvant into the right hindpaw which lead to the development of arthritic symptoms in all animals tested for antinociception. On day 11 after arthritis induction, mechanical hyperalgesia was assessed by the modified Randall Selitto paw pressure test following acute treatment with lacosamide. Lacosamide dose-dependently attenuated mechanical hyperalgesia following carrageenan injection and in rats suffering from Freund's complete adjuvant-induced arthritis. Moreover, thermal hyperalgesia induced by carrageenan as well as the formalin-induced licking response were dose-dependently attenuated by lacosamide. These results suggest lacosamide may be active against Various forms of acute and chronic inflammatory pain in humans. (c) 2005 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:241 / 249
页数:9
相关论文
共 23 条
[1]   LACK OF ANALGESIC EFFECT OF OPIOIDS ON NEUROPATHIC AND IDIOPATHIC FORMS OF PAIN [J].
ARNER, S ;
MEYERSON, BA .
PAIN, 1988, 33 (01) :11-23
[2]   Use of anticonvulsants for treatment of neuropathic pain [J].
Backonja, MM .
NEUROLOGY, 2002, 59 (05) :S14-S17
[3]   Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V) [J].
Bialer, M ;
Johannessen, SI ;
Kupferberg, HJ ;
Levy, RH ;
Loiseau, P ;
Perucca, E .
EPILEPSY RESEARCH, 2001, 43 (01) :11-58
[4]   A comparison of the anti-nociceptive effects of voltage-activated Na+ channel blockers in the formalin test [J].
Blackburn-Munro, G ;
Ibsen, N ;
Erichsen, HK .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 445 (03) :231-238
[5]   FURTHER EVIDENCE VALIDATING ADJUVANT ARTHRITIS AS AN EXPERIMENTAL-MODEL OF CHRONIC PAIN IN THE RAT [J].
COLPAERT, FC ;
MEERT, T ;
DEWITTE, P ;
SCHMITT, P .
LIFE SCIENCES, 1982, 31 (01) :67-75
[6]   FORMALIN TEST - QUANTITATIVE STUDY OF ANALGESIC EFFECTS OF MORPHINE, MEPERIDINE, AND BRAIN-STEM STIMULATION IN RATS AND CATS [J].
DUBUISSON, D ;
DENNIS, SG .
PAIN, 1977, 4 (02) :161-174
[7]   Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents [J].
Field, MJ ;
Oles, RJ ;
Lewis, AS ;
McCleary, S ;
Hughes, J ;
Singh, L .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 121 (08) :1513-1522
[8]   Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia [J].
Hurley, RW ;
Chatterjea, D ;
Feng, MHR ;
Taylor, CP ;
Hammond, DL .
ANESTHESIOLOGY, 2002, 97 (05) :1263-1273
[9]   PREPARATION AND ANTICONVULSANT ACTIVITY OF A SERIES OF FUNCTIONALIZED ALPHA-HETEROATOM-SUBSTITUTED AMINO-ACIDS [J].
KOHN, H ;
SAWHNEY, KN ;
LEGALL, P ;
ROBERTSON, DW ;
LEANDER, JD .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (08) :2444-2452
[10]   The thermal and mechanical anti-hyperalgesic effects of pre- versus post-intrathecal treatment with lamotrigine in a rat model of inflammatory pain [J].
Lee, TH ;
Wang, CJ ;
Wu, PC ;
Buerkle, H ;
Lin, SH ;
Yang, LC .
LIFE SCIENCES, 2002, 70 (25) :3039-3047