Beyreuther Bettina, Callizot Noëlle, Stöhr Thomas
Schwarz BioSciences GmbH, Department Pharmacology/Toxicology, Alfred-Nobel-Str. 10, 40789 Monheim, Germany.
Eur J Pharmacol. 2006 Jun 6;539(1-2):64-70. doi: 10.1016/j.ejphar.2006.04.009. Epub 2006 Apr 7.
Lacosamide was tested in the streptozotocin rat model of diabetic neuropathic pain in comparison to drugs which are commonly used in the treatment of diabetic neuropathic pain, i.e. antidepressants and anticonvulsants. In diabetic rats, lacosamide attenuated cold (10, 30 mg/kg, i.p.), warm (3, 10, 30 mg/kg, i.p.) and mechanical allodynia (30 mg/kg, i.p.). Streptozotocin-induced thermal and mechanical hyperalgesia were reduced by lacosamide at doses of 10 and 30 mg/kg, i.p. Morphine (3 mg/kg) showed similar efficacy on allodynia and hyperalgesia. Amitriptyline (10 mg/kg), venlafaxine (15 mg/kg), levetiracetam (180 mg/kg) and pregabalin (100 mg/kg) exhibited significant effects on thermal allodynia and mechanical hyperalgesia. Only treatment with amitriptyline (30 mg/kg, i.p.) produced full reversal of thermal allodynia comparable to lacosamide. Lamotrigine (45 mg/kg, i.p.) had no effect on both behavioral readouts. Lacosamide's potency and efficacy in reversing pain behavior might be due to its new, yet unknown mechanism of action.
与常用于治疗糖尿病性神经病理性疼痛的药物(即抗抑郁药和抗惊厥药)相比,拉科酰胺在链脲佐菌素诱导的糖尿病性神经病理性疼痛大鼠模型中进行了测试。在糖尿病大鼠中,拉科酰胺减轻了冷痛觉过敏(腹腔注射10、30mg/kg)、热痛觉过敏(腹腔注射3、10、30mg/kg)和机械性异常性疼痛(腹腔注射30mg/kg)。腹腔注射10和30mg/kg剂量的拉科酰胺可减轻链脲佐菌素诱导的热痛觉过敏和机械性痛觉过敏。吗啡(3mg/kg)对异常性疼痛和痛觉过敏显示出相似的疗效。阿米替林(10mg/kg)、文拉法辛(15mg/kg)、左乙拉西坦(180mg/kg)和普瑞巴林(100mg/kg)对热异常性疼痛和机械性痛觉过敏有显著影响。只有腹腔注射阿米替林(30mg/kg)能完全逆转热异常性疼痛,其效果与拉科酰胺相当。拉莫三嗪(腹腔注射45mg/kg)对两种行为学指标均无影响。拉科酰胺在逆转疼痛行为方面的效力和疗效可能归因于其新的、尚不清楚的作用机制。