Warren S, Lucchesi B R, Shlafer M
Res Commun Chem Pathol Pharmacol. 1979 Aug;25(2):227-39.
N-dimethyl propranolol (UM-272) has been shown to protect the heart from injury produced by ischemia. In the present study we examined the effects of UM-272 on the function of isolated rabbit cardiac mitochondria and microsomes. Concentrations of 13 micrometers or below were without effect on these organelles. UM-272 (130 micrometers) significantly decreased respiratory control of mitochondria utilizing glutamate plus malate, or succinate, as substrates. At 1.3 mM, UM-272 increased the initial rate of basal oxygen consumption, and decreased the rate of ADP-stimulated respiration. UM-272 was slightly more potent than d,1-propranolol. At a concentration of 1.3 mM, UM-272 significantly decreased the rate and maximum amount of 45CaCl2 accumulated by microsomes in the presence of ATP and oxalate. Concentrations of drug that suppress cellular metabolism are close to those required to prevent ischemic injury. We suggest that sarcolemmal and intracellular actions of the drug which help to depress oxygen demand and ATP utilization may account for part of the drug's protective effects.
N - 二甲基普萘洛尔（UM - 272）已被证明可保护心脏免受缺血造成的损伤。在本研究中，我们检测了UM - 272对分离的兔心脏线粒体和微粒体功能的影响。13微摩尔或更低的浓度对这些细胞器没有影响。UM - 272（130微摩尔）显著降低了以谷氨酸加苹果酸或琥珀酸为底物的线粒体的呼吸控制。在1.3毫摩尔时，UM - 272增加了基础氧消耗的初始速率，并降低了ADP刺激的呼吸速率。UM - 272的效力略强于消旋普萘洛尔。在1.3毫摩尔的浓度下，UM - 272显著降低了微粒体在ATP和草酸盐存在下积累45CaCl2的速率和最大量。抑制细胞代谢的药物浓度接近预防缺血性损伤所需的浓度。我们认为，该药物的肌膜和细胞内作用有助于降低氧需求和ATP利用，这可能是该药物部分保护作用的原因。
