ACADESINE - PROTOTYPE ADENOSINE REGULATING AGENT FOR TREATING MYOCARDIAL ISCHEMIA-REPERFUSION INJURY

被引:26
作者
MULLANE, K
YOUNG, M
机构
[1] Research Department, Gensia Pharmaceutical, Inc., San Diego
关键词
ISCHEMIA; CARDIAC SURGERY; CARDIOPROTECTION;
D O I
10.1002/ddr.430280327
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Acadesine is an adenosine regulating agent currently being developed for treatment of ischemia-reperfusion injury in the setting of cardiac surgery. While the cardioprotective effects of adenosine are well recognized, the intrinsic hemodynamic and cardiac effects of adenosine limit its potential usefulness as a therapeutic agent. In contrast, acadesine has been shown to elevate endogenous levels of adenosine during periods of ischemia without exhibiting systemic hemodynamic actions. The site-specific and event-specific mechanism of action thus provides cardioprotection without the adverse sequelae commonly observed with adenosine. This review describes the pertinent literature which establishes acadesine's action as an adenosine regulating agent, and discusses past and recent studies which focus on the cardioprotective actions of acadesine. These studies include in vitro and in vivo models of regional and global ischemia, and models of cardiac surgery. Aspects of dose-response, timing of administration, and pharmacokinetics of acadesine are described which reconcile prior controversy regarding acadesine's cardioprotective actions. These studies, taken together, demonstrate that acadesine is the prototype of a new class of adenosine regulating agents useful as therapy for cardiac ischemia.
引用
收藏
页码:336 / 343
页数:8
相关论文
共 40 条
  • [1] EFFECTS OF ATP PRECURSORS ON ATP AND FREE ADP CONTENT AND FUNCTIONAL RECOVERY OF POSTISCHEMIC HEARTS
    AMBROSIO, G
    JACOBUS, WE
    MITCHELL, MC
    LITT, MR
    BECKER, LC
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (02): : H560 - H566
  • [2] INHIBITION OF 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOTIDE TRANSFORMYLASE, ADENOSINE-DEAMINASE AND 5'-ADENYLATE DEAMINASE BY POLYGLUTAMATES OF METHOTREXATE AND OXIDIZED FOLATES AND BY 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBOSIDE AND RIBOTIDE
    BAGGOTT, JE
    VAUGHN, WH
    HUDSON, BB
    [J]. BIOCHEMICAL JOURNAL, 1986, 236 (01) : 193 - 200
  • [3] THE CARDIAC EFFECTS OF ADENOSINE
    BELARDINELLI, L
    LINDEN, J
    BERNE, RM
    [J]. PROGRESS IN CARDIOVASCULAR DISEASES, 1989, 32 (01) : 73 - 97
  • [4] CARDIAC NUCLEOTIDES IN HYPOXIA - POSSIBLE ROLE IN REGULATION OF CORONARY BLOOD FLOW
    BERNE, RM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1963, 204 (02): : 317 - &
  • [5] ACADESINE (AICA-RIBOSIDE) IMPROVES POSTISCHEMIC CARDIAC RECOVERY
    BOLLING, SF
    GROH, MA
    MATTSON, AM
    GRINAGE, RA
    GALLAGHER, KP
    [J]. ANNALS OF THORACIC SURGERY, 1992, 54 (01) : 93 - 98
  • [6] ATP PRECURSOR DEPLETION AND POSTISCHEMIC MYOCARDIAL RECOVERY
    BOLLING, SF
    BOVE, EL
    GALLAGHER, KP
    [J]. JOURNAL OF SURGICAL RESEARCH, 1991, 50 (06) : 629 - 633
  • [7] ENHANCED MYOCARDIAL PROTECTION WITH ADENOSINE
    BOLLING, SF
    BIES, LE
    GALLAGHER, KP
    BOVE, EL
    [J]. ANNALS OF THORACIC SURGERY, 1989, 47 (06) : 809 - 815
  • [8] BULLOUGH DA, 1992, J MOL CELL CARDIOL, V24, P56
  • [9] EFFECT OF ADENOSINE-DEAMINASE INHIBITORS ON THE HEART FUNCTIONAL AND BIOCHEMICAL RECOVERY FROM ISCHEMIA - A STUDY UTILIZING THE ISOLATED RAT-HEART ADAPTED TO P-31 NUCLEAR MAGNETIC-RESONANCE
    DHASMANA, JP
    DIGERNESS, SB
    GECKLE, JM
    NG, TC
    GLICKSON, JD
    BLACKSTONE, EH
    [J]. JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1983, 5 (06) : 1040 - 1047
  • [10] AICA-RIBOSIDE - SAFETY, TOLERANCE, AND PHARMACOKINETICS OF A NOVEL ADENOSINE-REGULATING AGENT
    DIXON, R
    GOURZIS, J
    MCDERMOTT, D
    FUJITAKI, J
    DEWLAND, P
    GRUBER, H
    [J]. JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 31 (04) : 342 - 347