Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain.
Lacosamide is a functionalized amino acid which was initially synthesized as an antiepileptic drug. In addition to its broad anti-seizure activity, lacosamide was 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.
Stöhr
Thomas
T
Schwarz BioSciences GmbH, Department of Pharmacology/Toxicology, Alfred-Nobel Street 10, 40789 Monheim, Germany. thomas.stoehr@schwarzpharma.com
Krause
Eva
E
Selve
Norma
N
D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy*; D002351:Carrageenan; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D000078334:Lacosamide; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011930:Reaction Time; D014110:Touch
D000081:Acetamides; D005557:Formaldehyde; D000078334:Lacosamide; D002351:Carrageenan