Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912, USA.
Pharmacotherapy. 2010 Jul;30(7 Pt 2):55S-61S. doi: 10.1592/phco.30.pt2.55S.
Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.
组织型纤溶酶原激活物（tPA）是唯一经美国食品和药物管理局批准用于治疗急性缺血性脑卒中的药物。由于该药必须在症状发作后尽快使用，且与脑出血相关，因此 tPA 的应用仍不充分。因此，研究的重点是确定其他可与 tPA 联合使用的药物，以提高有利恢复的几率，并降低脑出血的风险。米诺环素是一种广谱抗生素，在临床前缺血性脑卒中模型中被发现具有神经保护作用。米诺环素可抑制基质金属蛋白酶-9，这是与 tPA 使用相关的脑出血的生物标志物。米诺环素也是一种抗炎剂，可抑制多聚（ADP-核糖）聚合酶-1。米诺环素在临床试验中是安全且耐受良好的。还需要更多的安全性和疗效数据，一项关于米诺环素与 tPA 联合治疗急性缺血性脑卒中患者的 III 期试验正在计划中。
