Normalizing effect of energy metabolism regulator (succinic acid) on mitochondrial processes in rat myocardium during hypoxia, cardiac arrhythmia, and salicylate treatment was experimentally shown. A new alternative method for myocardial protection is proposed and its high efficiency in heart diseases of hypoxic and ischemic origin is validated. Address for correspon dence: vkh@pharm.tsu.ru. V. A. Khazanov Coronary disease developing as a result of coronary atherosclerosis is the leading cause of disability and mortality of population of capable age [7]. The progress of atherosclerosis in coronary arteries leads to a discrepancy between the level of coronary bloodflow and myocardial demands for oxygen and substrates associated with augmenting ischemia and hypoxia in cardiomyocytes, this leading to drastic changes in metabolism and energy supply [11]. Inhibition of ATP and creatinine phosphate synthesis associated with this condition leads to disorders in heart rhythm and myocardial contractility.Drug therapy of myocardial ischemia consists in increasing O 2 delivery to the ischemic zone or reducing the O 2 demands of the myocardium. β-Adrenoreceptor blockers, nitrates, angiotensin-converting enzyme inhibitors, calcium antagonists, metabolic drugs, and antiaggregants are used for this purpose [7,8].One of the main drugs for metabolic therapy of coronary disease is trimetazidine (TZ), a selective inhibitor of long-chain 3-ketoacyl-CoA-thiolase [8].It inhibits β-oxidation of fatty acids without inhibition glycolysis, which creates metabolic prerequisites for lactate utilization and reduction of lactoacidosis in the ischemic myocardium. In addition, TZ partially reduces activity of phospholipase A 2 and LPO intensity, which in general leads to improvement of the myocardial function. However, TZ does not completely eliminate the hypoxic type of metabolism. Presumably, blockade of one of the most effective metabolic pathways of energy supply to the myocardium (lipid utilization) limits the potentialities of therapy for the diseases associated with the development of the deficiency of highenergy metabolites [11]. We proposed a principally new pharmacological approach to cardiac protection, consisting in removal of the metabolic limitations of ATP production in the ischemic myocardium without negative impact on the metabolism.We proposed a new class of drugs regulating energy metabolism, optimizing energy supply processes, including those in the ischemic myocardium [11,13]. These drugs provide ATP production in cells at the expense of activity of the rapid metabolic cluster in mitochondria [12,13]. We previously showed that energy metabolism regulators reduced toxicity and increased the efficiency of acetylsalicylic acid (ASA) widely used in cardiology as an antiaggregant [2,7].

An important stage in the preclinical study of a new drug is the study of its pharmacokinetics: absorption, distribution, metabolism, and excretion of the drug compound. The purpose of this study was to study the pharmacokinetics in healthy animals of a new analgesic based on hexaazaisowurtzitane (thiowurtzine). Materials and methods. A technique for determining the concentration of thiowurtzine in the blood plasma and rat excreta has been developed and validated. Using high-performance liquid chromatography and tandem mass spectrometry, concentrations of thiowurtzine in plasma and rat excreta were determined after a single intragastric dose of 100 mg/kg. Results. The peak concentration of thiowurtzine in the blood plasma of rats accounts for 2 hours, which is consistent with the pharmacodynamic data of the analgesic, the average retention time of the substance in the body reached 17.15 h after administration. Thiowurtzine is believed to be actively metabolized.

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