MC-1 (pyridoxal 5′-phosphate):: novel therapeutic applications to reduce ischaemic injury
MC-1 (pyridoxal 5′-phosphate):: novel therapeutic applications to reduce ischaemic injury
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DOI：
10.1517/13543784.14.11.1435
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Harrington, RA
中科院分区：
文献类型：
--
作者：
Kandzari, DE;Dery, JP;Harrington, RA
尽管机械再灌注疗法（例如经皮冠状动脉介入治疗和冠状动脉搭桥手术）在降低与急性缺血综合征相关的发病率和死亡率方面具有总体疗效，但许多接受治疗的患者由于微血管完整性受损、动脉粥样硬化血栓碎片栓塞和/或破坏而发生缺血再灌注损伤。 终末器官代谢。 MC-1 是 Medicure, Inc. 的一种在缺血和缺血再灌注损伤临床前模型中进行研究的药物，MC-1 治疗已显示出显着的心脏和神经保护作用。尽管 MC-1 的药理活性可能涉及多种机制，但研究表明至少部分保护作用可能是通过其对嘌呤能受体的作用来介导的。 MC-1 的早期临床经验似乎也很有希望：在最近的 11 期评估中，在接受选择性经皮冠状动脉介入治疗的高危患者中，MC-1 治疗与围手术期梗死面积（按肌酸激酶心肌带曲线下面积测量）统计显着减少相关。基于这些发现，正在进行或正在开展更大规模的随机试验，以确认 MC-1 在冠状动脉旁路移植术、急性冠状动脉综合征和中风的冠状动脉血运重建中的安全性和有效性。这些即将进行的评估应阐明 MC-1 的安全性和有效性，并增进对其在各种临床环境和适应症中潜在治疗作用的理解。
Despite the overall efficacy of mechanical reperfusion therapies, such as percutaneous coronary intervention and coronary artery bypass graft surgery, in reducing the morbidity and mortality that is associated with acute ischaemic syndromes, many of the treated patients develop ischaemia-reperfusion injury due to impaired microvascular integrity, embolisation of atherothrombotic debris and/or disrupted end-organ metabolism. MC-1 is an investigational drug from Medicure, Inc. in preclinical models of ischaemia and ischaemia-reperfusion injury, treatment with MC-1 has demonstrated significant cardio- and neuroprotective effects. Although the pharmacological activity of MC-1 may involve multiple mechanisms, research suggests that at least part of the protective effect may be mediated through its actions on purinergic receptors. Early clinical experience with MC-1 also appears to be promising: in a recent Phase 11 evaluation, treatment with MC-1 was associated with a statistically significant reduction in periprocedural infarct size (as measured by area under the curve creatine kinase-myocardial band) among high-risk patients undergoing elective percutaneous coronary intervention. Based on these findings, larger, randomised trials to confirm the safety and efficacy of MC-1 in the setting of coronary artery revascularisation with coronary artery bypass graft, acute coronary syndromes and stroke are ongoing or in development. These forthcoming evaluations should clarify the safety and efficacy of MC-1 and improve the understanding regarding its potential therapeutic role in a variety of clinical settings and indications.