Mechanism of protective effect of energostim during catalepsy produced by single treatment with trifluoperazine.

NAD, cytochrome c, and energostim modulated the fluorescence emission spectrum of trifluoperazine in the solution and in microsomal suspension. The data suggest that NAD and energostim modify structural and conformational characteristics of the dopamine receptor-trifluoperazine complex. These changes probably underlie the anticataleptic effect of energostim.

Anticataleptic effect of energostim during single treatment with trifluoperazine.

Administration of trifluoperazine in a single dose of 3 mg/kg induced catalepsy and locomotor disorders in 86% intact animals, which persisted for 4 h. Catalepsy developed in only 15% animals pretreated with antihypoxic and antioxidant agent energostim in a dose of 230 mg/kg. The protective effect of energostim was associated with its ability to maintain the balance between dopaminergic, cholinergic, and adrenal activity in the substantia nigra and medulla oblongata during administration of neuroleptics.

[Cardioprotective effect of energostim in toxic allergic myocarditis]. / Kardioprotektornoe deistvie énergostima pri toksiko-allergicheskom miokardite.

Energostim is a combined drug comprising a mixture of nicotinamide adenine dinucleotide (0.5 mg), cytochrome C (10 mg), and inosine (80 mg), representing antihypoxant and antioxidant of direct action in one ampule. After pretreatment and subsequent 3-day energostim therapy of animals with 3-day toxico-allergic myocarditis (3d-TAM), the ECG was free of any rhythm disorders and showed evidence of improved conduction, restoration of the normal form of T-wave and the position of ST segment, while the content of myofibrillar fraction of creatine phosphokinase and toxic products of disturbed metabolism (degree of endotoxemia) decreased to the upper normal level. Under the action of energostim, neither pressure nor the maximum rate of pressure buildup in the left ventricle are reduced (as they do upon 3d-TAM); neither systolic and diastolic functions are disturbed, nor their coordination (r = 0.79 between dP/dtmin and dP/dtmax, p < 0.01). The restoration of contractile activity and maximum rate of relaxation of myocardial microfibrils during 3d-TAM is accompanied by an increase in the content of adenyl nucleotides, in the ATP/ADP, ADP/AMP, NAD/NADH, and NADP/NADPH ratios, and in the cytosol phosphorylation potential. The energostim-induced improvement in the energy supply system are accompanied by restoration of the ability of sarcoplasmic reticulum to efflux Ca2+. Thus, it is demonstrated that the effect of energostim is related to its ability to actively participate in intracell metabolic processes in myocardium, abolish necrotic changes and endotoxicosis, and restore homeostasis in the systems responsible for the contraction--relaxation process (thus preventing from the development of dysfunction of the left ventricle and the heart failure).

Effect of richlocaine alone or in combination with energostim on the severity of endotoxemia and survival of the skin under conditions of reduced blood flow.

The local anesthetic richlocaine decreased the area of necrosis in the skin flap under conditions of reduced blood flow by 29.5%. Improved survival of skin flap after richlocaine treatment alleviated endogenous intoxication, reduced secondary inflammatory reaction, improved liver function, and normalized the ratio between vasoconstricting and vasodilating prostaglandins. This effect was most pronounced after combination therapy with richlocaine and direct-action antihypoxant energostim.

Cardioprotective effect of energostim during occlusion of coronary artery.

Experiments on dogs showed that energostim, a directly acting antihypoxant, injected 15 min after occlusion of the upper one-third of the left descending branch of the interventricular coronary artery produced a pronounced cardioprotective effect. The effect was confirmed by electron microscopy (evaluation the necrotic focus), biochemical tests of the heart and blood, and changes in intracardiac hemodynamics (recovery of systolic and diastolic functions). The cardioprotective effect of energostim greatly surpasses that of routine therapy applied during acute myocardium infarction.

Effects of energostim on the sympathoadrenal system and contents of pyridine nucleotides during acute myocardial infarction.

The contents of myofibrillar creatine phosphokinase and cytochrome c, the key enzyme of the mitochondrial respiratory chain, increased, while the content of nicotinamide coenzymes and redox potential (NAD/NADH ratio) sharply decreased over the first 6 h of acute myocardial infarction. The contents of norepinephrine and epinephrine increased by 51 and 49%, respectively, 6 h after onset of acute myocardial infarction. By contrast, dopamine concentration decreased by 116% during this period. The increase in the content of cytochrome c directly correlated with the concentration of myofibrillar creatine phosphokinase and Peel index. No correlations were found between norepinephrine/epinephrine and dopamine/(norepinephrine+epinephrine) ratios. The antihypoxant with direct action energostim normalized the content of cytochrome c, increased NAD and dopamine concentrations and NAD/NADH ratio, and decreased the content of norepinephrine and epinephrine to the baseline level in patients with acute myocardial infarction. These results indicate that energostim possesses not only antihypoxic and antioxidant activities, but also pronounced antisympathomimetic properties.