Ranolazine: A novel metabolic modulator for the treatment of angina

被引:67
作者
McCormack, JG
Stanley, WC
Wolff, AA
机构
[1] CV Therapeut, Palo Alto, CA 94304 USA
[2] Novo Nordisk AS, Diabet Discovery, DK-2880 Bagsvaerd, Denmark
[3] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA
来源
GENERAL PHARMACOLOGY-THE VASCULAR SYSTEM | 1998年 / 30卷 / 05期
关键词
ranolazine; angina; cardiac; coronary artery disease; fatty acids; heart; ischemia; lactate; myocardial metabolism; pyruvate dehydrogenase; beta-oxidation; skeletal muscle;
D O I
10.1016/S0306-3623(97)00301-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. Ranolazine shifts ATP production away from fatty acid oxidation toward glucose oxidation. 2. Because more oxygen is required to phosphorylate a given amount of ATP during fatty acid oxidation than during carbohydrate oxidation, the ranolazine-induced shift in substrate selection reduces the cell's demand for oxygen without decreasing its ability to do work. The shift also maintains coupling of glycolysis to glucose oxidation during ischemia, thus reducing tissue acidosis, 3. This unique, non-hemodynamic mechanism offers the potential to treat angina without reducing blood pressure, heart rate or myocardial contractility. 4. At least three double-blind, randomized, placebo-controlled clinical trials have yielded data consistent with this hypothesis. (C) 1998 Elsevier Science Inc.
引用
收藏
页码:639 / 645
页数:7
相关论文
共 37 条
[1]   Effects of ranolazine on the exercise capacity of rats with chronic heart failure induced by myocardial infarction [J].
Aaker, A ;
McCormack, JG ;
Hirai, T ;
Musch, TI .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1996, 28 (03) :353-362
[2]   PREVENTION OF MYOCARDIAL ENZYME-RELEASE BY RANOLAZINE IN A PRIMATE MODEL OF ISCHEMIA WITH REPERFUSION [J].
ALLELY, MC ;
ALPS, BJ .
BRITISH JOURNAL OF PHARMACOLOGY, 1990, 99 (01) :5-6
[3]   THE EFFECTS OF THE NOVEL ANTI-ANGINAL AGENT RS-43285 ON [LACTIC-ACID], [K+] AND PH IN A CANINE MODEL OF TRANSIENT MYOCARDIAL ISCHEMIA [J].
ALLELY, MC ;
ALPS, BJ ;
KILPATRICK, AT .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1987, 15 (06) :1057-1058
[4]   A COMPARISON OF THE EFFECTS OF A SERIES OF ANTI-ANGINAL AGENTS IN A NOVEL CANINE MODEL OF TRANSIENT MYOCARDIAL ISCHEMIA [J].
ALLELY, MC ;
ALPS, BJ .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 96 (04) :977-985
[5]   MODULATION OF ALPHA(1)-ADRENOCEPTORS IN RAT LEFT-VENTRICLE BY ISCHEMIA AND ACYL CARNITINES - PROTECTION BY RANOLAZINE [J].
ALLELY, MC ;
BROWN, CM ;
KENNY, BA ;
KILPATRICK, AT ;
MARTIN, A ;
SPEDDING, M .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1993, 21 (06) :869-873
[6]   EFFECT OF RANOLAZINE ON INFARCT SIZE IN A CANINE MODEL OF REGIONAL MYOCARDIAL ISCHEMIA/REPERFUSION [J].
BLACK, SC ;
GRALINSKI, MR ;
MCCORMACK, JG ;
DRISCOLL, EM ;
LUCCHESI, BR .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1994, 24 (06) :921-928
[7]   NEW ANTI-ISCHAEMIC DRUGS - CYTOPROTECTIVE ACTION WITH NO PRIMARY HEMODYNAMIC-EFFECTS [J].
BODDEKE, E ;
HUGTENBURG, J ;
JAP, W ;
HEYNIS, J ;
VANZWIETEN, P .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1989, 10 (10) :397-400
[8]   BENEFICIAL EFFECT OF CARNITINE ON MECHANICAL RECOVERY OF RAT HEARTS REPERFUSED AFTER A TRANSIENT PERIOD OF GLOBAL-ISCHEMIA IS ACCOMPANIED BY A STIMULATION OF GLUCOSE-OXIDATION [J].
BRODERICK, TL ;
QUINNEY, HA ;
BARKER, CC ;
LOPASCHUK, GD .
CIRCULATION, 1993, 87 (03) :972-981
[9]   METABOLIC MANAGEMENT OF ISCHEMIC-HEART-DISEASE [J].
CHIERCHIA, SL ;
FRAGASSO, G .
EUROPEAN HEART JOURNAL, 1993, 14 :2-5
[10]   PROTECTIVE EFFECTS OF RANOLAZINE IN GUINEA-PIG HEARTS DURING LOW-FLOW ISCHEMIA AND THEIR ASSOCIATION WITH INCREASES IN ACTIVE PYRUVATE-DEHYDROGENASE [J].
CLARKE, B ;
SPEDDING, M ;
PATMORE, L ;
MCCORMACK, JG .
BRITISH JOURNAL OF PHARMACOLOGY, 1993, 109 (03) :748-750