| 摘要 |
A pharmaceutical composition, useful for reducing tissue damage resulting from ischemica, comprises a sodium- hydrogen exchanger type-1 inhibitor and either: (a) a complement modulator, (b) a metabolic modulator, (c) an anti-apoptotic agent, (d) a nitric oxide synthase-related agent, or (e) an enzyme/protein modulator The sodium-hydrogen exchanger type-1 inhibitor is (i) a compound of formula (I) or a prodrug or a pharmaceutically acceptable salt thereof wherein Z is carbon connected optionally mono-, di-, or tri-substituted five- membered, diaza, or triaza di-unsaturated ring with the diaza ring having two contiguous nitrogens; (ii) cariporide, or a pharmaceutically acceptable salt thereof; (iii) eniporide, or a pharmaceutically acceptable salt thereof; (iv) BIIB 513, or a pharmaceutically acceptable salt thereof; (v) TY-12533, or a pharmaceutically acceptable salt thereof; or (vi) SM-15681, or a pharmaceutically acceptable salt thereof. The complement modulator is a C5a inhibitor, a soluble complement receptor type 1 (sCR1) inhibitor or a C1-esterase inhibitor. The metabolic modulator is a pyruvate dehydrogenase complex up-regulator/activator, a pyruvate dehydrogenase kinase inhibitor, a malonyl CoA decarboxylase inhibitor, an acetyl CoA carboxylase activator, a partial fatty acid oxidation (pFOX) inhibitor, a 5' AMP-activated protein kinase (AMPK) inhibitor, a carnitine palmitoyl transferase inhibitor, or a fatty acid CoA synthase inhibitor. The anti-apoptotic agent is a caspase inhibitor. The nitric oxide synthase-related agent is monophosporyl lipid A, or an analog thereof, a nitric oxide donor, or a nitric oxide synthase activator. The enzyme/protein modulator is a protein kinase C activator, an endothelin converting enzyme inhibitor, a tissue-activated fibrinolytic inhibitor (TAFI), a Na+/Ca2+- exchanger isoform-1 (NCX-1) inhibitor, or a poly (ADP ribose) synthetase (PARS/PARP) inhibitor.
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