Antinociceptive efficacy of lacosamide in rat models for tumor- and chemotherapy-induced cancer pain.
Pain is the most common physical symptom of cancer patients, with most patients experiencing more than one site of pain. Current treatments lack full efficacy. Based on the need for new approaches in that field the effect of systemic administration of lacosamide (SPM 927, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037), a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsive drug candidates, was examined in rats in a tumor-induced bone cancer pain model and in a chemotherapy-induced neuropathic pain model. Lacosamide inhibited tactile allodynia (20, 40 mg/kg, i.p.), thermal hyperalgesia (30 mg/kg) and reduced weight-bearing differences (40 mg/kg) in the rat model of bone cancer pain induced by injection of MRMT-1 cells into the tibia. Morphine (5 mg/kg, s.c) was effective inhibiting tactile allodynia and weight bearing but could not reduce thermal hyperalgesia. In the vincristine-induced neuropathic pain model, lacosamide attenuated thermal allodynia, on the cold plate (4 degrees C), at 10 and 30 mg/kg, and in the warm (38 degrees C) and hot plate (52 degrees C) even at 3 mg/kg. Tactile allodynia and mechanical hyperalgesia were inhibited by lacosamide at 10 and 30 mg/kg. In contrast to lacosamide, morphine (3 mg/kg, s.c.) had no effect on mechanical hyperalgesia. Lacosamide is effective as an analgesic in a bone cancer pain model as well as chemotherapy-induced neuropathic pain model in animals and even reduced hyperalgesia where morphine did not (3 or 5 mg/kg, s.c.).
Beyreuther
Bettina K
BK
Schwarz BioSciences GmbH, Department of Pharmacology/Toxicology, Alfred-Nobel-Str. 10, 40789 Monheim, Germany. bettina.beyreuther@schwarzpharma.com
Callizot
Noëlle
N
Brot
Michelle D
MD
Feldman
Rachel
R
Bain
Steven C
SC
Stöhr
Thomas
T
D000081:Acetamides / Q000627:therapeutic use*; D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001859:Bone Neoplasms / Q000503:physiopathology*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D005260:Female; D000077206:Gabapentin; D000078334:Lacosamide; D009437:Neuralgia / Q000188:drug therapy*; D010148:Intractable Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014750:Vincristine / Q000633:toxicity*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000081:Acetamides; D000588:Amines; D000700:Analgesics; D000972:Antineoplastic Agents, Phytogenic; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000078334:Lacosamide; D014750:Vincristine; D000077206:Gabapentin