Complex electrophysiological study of the effects of quaternidine carried out on intact hearts from cats, myocardial fragments from rats, and single ionic channels of large edible snail showed that quaternidine demonstrates properties of class 1B antiarrhythmic drug according to Vaughan-Williams nomenclature. This agent did not suppress nomotopic pacemaker automaticity, did not change conduction in ventricles, atria, and atrioventricular junction in hearts with preserved sinus rhythm, did not prolong refractoriness of the atria and atrioventricular junction, but prolonged efficient refractory period of heart ventricles. Quaternidine decelerated rapid depolarization of the action potential, but had no effect on its duration. It did not affect potassium conductance.

A non-surgical pharmacological approach to control cellular vitality and functionality during ischemic and/or reperfusion-induced phases of strokes remains extremely important. The synthesis of 2-ethyl-6-methyl-3-hydroxypyridinium gammalactone-2,3-dehydro-L-gulonate (3-EA) was performed using a topochemical reaction. The cell-protective effects of 3-EA were studied on a model of glutamate excitotoxicity (GluTox) and glucose-oxygen deprivation (OGD) in a culture of NMRI mice cortical cells. Ca2+ dynamics was studied using fluorescent bioimaging and a Fura-2 probe, cell viability was assessed using cytochemical staining with propidium iodide, and gene expression was assessed by a real-time polymerase chain reaction. The compound anti-ischemic efficacy in vivo was evaluated on a model of irreversible middle cerebral artery (MCA) occlusion in Sprague-Dawley male rats. Brain morphological changes and antioxidant capacity were assessed one week after the pathology onset. The severity of neurological disorder was evaluated dynamically. 3-EA suppressed cortical cell death in a dose-dependent manner under the excitotoxic effect of glutamate and ischemia/reoxygenation. Pre-incubation of cerebral cortex cells with 10–100 µM 3-EA led to significant stagnation in Ca2+ concentration in a cytosol ([Ca2+]i) of neurons and astrocytes suffering GluTox and OGD. Decreasing intracellular Ca2+ and establishing a lower [Ca2+]i baseline inhibited necrotic cell death in an acute experiment. The mechanism of 3-EA cytoprotective action involved changes in the baseline and ischemia/reoxygenation-induced expression of genes encoding anti-apoptotic proteins and proteins of the oxidative status; this led to inhibition of the late irreversible stages of apoptosis. Incubation of brain cortex cells with 3-EA induced an overexpression of the anti-apoptotic genes BCL-2, STAT3, and SOCS3, whereas the expression of genes regulating necrosis and inflammation (TRAIL, MLKL, Cas-1, Cas-3, IL-1β and TNFa) were suppressed. 3-EA 18.0 mg/kg intravenous daily administration for 7 days following MCA occlusion preserved rats’ cortex neuron population, decreased the severity of neurological deficit, and spared antioxidant capacity of damaged tissues. 3-EA demonstrated proven short-term anti-ischemic activity in vivo and in vitro, which can be associated with antioxidant activity and the ability to target necrotic and apoptotic death. The compound may be considered a potential neuroprotective molecule for further pre-clinical investigation.

Data on the syntheses and structures of a series of new derivatives of 2-diethylamino-2¢,6¢-dimethylphenylacetamide are described. The results of an experimental study of the new compounds on various arrhythmia models in animals are presented. Several substances effectively preventing the onset of ventricular ischemia, reperfusive and toxic fibrillation, and ischemic arrhythmia have been selected, which are superior to the reference drug lidocaine with respect to their antiarrhythmic properties.

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