Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain

Abstract

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.

Anticonvulsant and antinociceptive activity of new amides derived from 3-phenyl-2,5-dioxo-pyrrolidine-1-yl-acetic acid in mice

“…In our previous study, we reported that the novel antiepileptic drug -lacosamide also displayed antinociceptive effect in both phases of the formalin test . Lacosamide, as well as tiagabine displayed analgesic effect in this test also in research conducted by other groups (Beyreuther et al, 2006;Laughlin et al, 2002;Stöhr et al, 2006). On the other hand, lamotrigine and gabapentin inhibited only the late phase formalin-induced behavior (Field et al, 1997;Laughlin et al, 2002).…”

Competitive Gly/NMDA Receptor Antagonists

“…Patent literature as well indicate the glycine site as the possible target of this compound [77]. In contrast, other recent publications do not report the precise mechanism of action of SPM-927 underlying the failure in the identification of a high affinity binding site [78][79][80].…”

“…The continued clinical development of SPM-927 was supported by numerous studies on the tolerability and effectiveness of this drug for the treatment of neuropathic pain [80,82] and epilepsy [78,79].…”

Lacosamida en el tratamiento del dolor neuropático

“…Pero parece que el efecto de alivio del dolor obtenido con lacosamida no está restringido al dolor neuropático. También puede tener un efecto sobre el dolor inflamatorio, como se ha demostrado en diferentes modelos animales (23)(24)(25)(26). En estudios en humanos, la mayoría de los trabajos publicados se han hecho en neuropatía diabética dolorosa.…”