MC-1 (pyridoxal 5′-phosphate):: novel therapeutic applications to reduce ischaemic injury

被引:21
作者
Kandzari, DE [1 ]
Dery, JP [1 ]
Armstrong, PW [1 ]
Douglas, DA [1 ]
Zettler, ME [1 ]
Hidinger, GKG [1 ]
Friesen, AD [1 ]
Harrington, RA [1 ]
机构
[1] Duke Clin Res Inst, Durham, NC 27705 USA
关键词
coronary revascularisation; ischaemia-reperfusion injury; P2-purinergic receptors; pyridoxal 5 '-phosphate; stroke;
D O I
10.1517/13543784.14.11.1435
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:1435 / 1442
页数:8
相关论文
共 53 条
[41]   Leukocyte adhesion to the coronary microvasculature during ischemia and reperfusion in an in vivo canine model [J].
Sheridan, FM ;
Cole, PG ;
Ramage, D .
CIRCULATION, 1996, 93 (10) :1784-1787
[42]   IN-VITRO STUDIES OF RELEASE OF ADENINE-NUCLEOTIDES AND ADENOSINE FROM RAT VASCULAR ENDOTHELIUM IN RESPONSE TO ALPHA(1)-ADRENOCEPTOR STIMULATION [J].
SHINOZUKA, K ;
HASHIMOTO, M ;
MASUMURA, S ;
BJUR, RA ;
WESTFALL, DP ;
HATTORI, K .
BRITISH JOURNAL OF PHARMACOLOGY, 1994, 113 (04) :1203-1208
[43]   Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention [J].
Tardiff, BE ;
Califf, RM ;
Tcheng, JE ;
Lincoff, AM ;
Sigmon, KN ;
Harrington, RA ;
Mahaffey, KW ;
Ohman, EM ;
Teirstein, PS ;
Blankenship, JC ;
Kitt, MM ;
Topol, EJ .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1999, 33 (01) :88-96
[44]   P-2 PURINOCEPTOR ANTAGONIST PROPERTIES OF PYRIDOXAL-5-PHOSPHATE [J].
TREZISE, DJ ;
BELL, NJ ;
KHAKH, BS ;
MICHEL, AD ;
HUMPHREY, PPA .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 259 (03) :295-300
[45]   PYRIDOXAL PHOSPHATE BREAKDOWN BY AN ALKALINE-PHOSPHATASE PREPARATION [J].
TURNER, JM .
BIOCHEMICAL JOURNAL, 1961, 80 (03) :663-+
[46]   Adenosine 5′-triphosphate:: a P2-Purinergic agonist in the myocardium [J].
Vassort, G .
PHYSIOLOGICAL REVIEWS, 2001, 81 (02) :767-806
[47]   ACTIVE SITE-DIRECTED INHIBITION OF E-COLI DNA-DEPENDENT RNA-POLYMERASE BY PYRIDOXAL 5'- PHOSPHATE [J].
VENEGAS, A ;
MARTIAL, J ;
VALENZUELA, P .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1973, 55 (04) :1053-1059
[48]  
VENTURA MA, 1995, MOL PHARMACOL, V47, P104
[49]   Differential distribution of two ATP-gated ion channels (P-2X receptors) determined by immunocytochemistry [J].
Vulchanova, L ;
Arvidsson, U ;
Riedl, M ;
Wang, J ;
Buell, G ;
Surprenant, A ;
North, RA ;
Elde, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :8063-8067
[50]   Role of MC-1 alone and in combination with tissue plasminogen activator in focal ischemic brain injury in rats [J].
Wang, CX ;
Yang, T ;
Noor, R ;
Shuaib, A .
JOURNAL OF NEUROSURGERY, 2005, 103 (01) :165-169