Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY29355 8, an α amino 3 hydroxy 5 methyl 4 isox azolepropionic acid (AMPA)/kain ate (KA) receptor antagonist, is effective in preclinical models ...Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY29355 8, an α amino 3 hydroxy 5 methyl 4 isox azolepropionic acid (AMPA)/kain ate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple blind, parallel group, double d ummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneou s (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary e fficacy variable was the headache response rate, i.e. headache score improvement from mod erate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients , 44 patients (20M:24F; mean age ±.SD = 40 ±.9 years) completed the study. Res ponse rates were 69%for LY293558 (P = 0.017 vs. placebo), 86%for sumatriptan ( P < .0.01 vs. placebo) and 25%for placebo. LY293558 and sumatriptan were superi or to placebo (P < .0.01 for all comparisons) on all other measures of improveme nt in pain and migraine associated symptoms. Fifteen percent of patients who too k LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty t hree percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31%of those who received placebo reported AEs (n = 5; four mild, one severe ). The efficacy and safety results of LY293558 in this small migraine proof of c oncept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.展开更多
目的通过比较常规开颅减压和控制减压两种不同手术减压方式对治疗兔重型颅脑外伤后急性颅内高压脑组织中海人藻受体亚基5(GluR5)和海人藻受体亚基6(GluR6)的表达水平及脑组织微观病理变化,探讨控制减压技术治疗重型颅脑伤的可能机制,为...目的通过比较常规开颅减压和控制减压两种不同手术减压方式对治疗兔重型颅脑外伤后急性颅内高压脑组织中海人藻受体亚基5(GluR5)和海人藻受体亚基6(GluR6)的表达水平及脑组织微观病理变化,探讨控制减压技术治疗重型颅脑伤的可能机制,为控制减压手术方法在临床应用提供理论依据。方法采用硬膜外球囊加压方法制备兔重型颅脑外伤后急性颅内高压的动物模型,新西兰白兔随机分为假手术组、控制减压组和常规减压组,观察术后24 h GluR5和GluR6的表达情况、术后兔脑组织HE染色、术后24 h ICP变化情况及术后兔头颅CT的变化。结果术后24 h,控制减压组GluR5的表达明显高于常规减压组(P<0.05),GluR6的表达明显低于常规减压组(P<0.05);脑组织HE染色控制减压组明显轻于常规减压组;控制减压组术后24 h ICP值明显低于常规减压组(P<0.05);控制减压组的脑梗塞发生率(10.5%)明显低于常规减压组(35.2%)(P<0.05)。结论控制减压模式治疗兔重型颅脑外伤能有效减轻脑缺血再灌注损伤(cerebral ischemia-reperfusion injury,I/R),降低术后脑梗塞等并发症发生率,起到明显的脑保护作用。展开更多
文摘Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY29355 8, an α amino 3 hydroxy 5 methyl 4 isox azolepropionic acid (AMPA)/kain ate (KA) receptor antagonist, is effective in preclinical models of migraine. We therefore tested LY293558 in acute migraine. We conducted a randomized, triple blind, parallel group, double d ummy, multicentre trial of 1.2 mg/kg intravenous (IV) LY293558, 6 mg subcutaneou s (SC) sumatriptan, or placebo in the treatment of acute migraine. The primary e fficacy variable was the headache response rate, i.e. headache score improvement from mod erate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients , 44 patients (20M:24F; mean age ±.SD = 40 ±.9 years) completed the study. Res ponse rates were 69%for LY293558 (P = 0.017 vs. placebo), 86%for sumatriptan ( P < .0.01 vs. placebo) and 25%for placebo. LY293558 and sumatriptan were superi or to placebo (P < .0.01 for all comparisons) on all other measures of improveme nt in pain and migraine associated symptoms. Fifteen percent of patients who too k LY293558 reported adverse events (AEs) (n = 2; one mild, one severe). Fifty t hree percent of patients who took sumatriptan (n = 8; seven mild, one moderate) and 31%of those who received placebo reported AEs (n = 5; four mild, one severe ). The efficacy and safety results of LY293558 in this small migraine proof of c oncept trial, together with supportive preclinical data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine. Larger trials are needed to further test the hypothesis.
文摘目的通过比较常规开颅减压和控制减压两种不同手术减压方式对治疗兔重型颅脑外伤后急性颅内高压脑组织中海人藻受体亚基5(GluR5)和海人藻受体亚基6(GluR6)的表达水平及脑组织微观病理变化,探讨控制减压技术治疗重型颅脑伤的可能机制,为控制减压手术方法在临床应用提供理论依据。方法采用硬膜外球囊加压方法制备兔重型颅脑外伤后急性颅内高压的动物模型,新西兰白兔随机分为假手术组、控制减压组和常规减压组,观察术后24 h GluR5和GluR6的表达情况、术后兔脑组织HE染色、术后24 h ICP变化情况及术后兔头颅CT的变化。结果术后24 h,控制减压组GluR5的表达明显高于常规减压组(P<0.05),GluR6的表达明显低于常规减压组(P<0.05);脑组织HE染色控制减压组明显轻于常规减压组;控制减压组术后24 h ICP值明显低于常规减压组(P<0.05);控制减压组的脑梗塞发生率(10.5%)明显低于常规减压组(35.2%)(P<0.05)。结论控制减压模式治疗兔重型颅脑外伤能有效减轻脑缺血再灌注损伤(cerebral ischemia-reperfusion injury,I/R),降低术后脑梗塞等并发症发生率,起到明显的脑保护作用。
