Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions.

This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds L and L, with L inducing temporary bradycardia and hypotension specifically in female rats, and L causing significant blood pressure reduction followed by rebound in females compared to milder effects in males.

Synthesis, Pharmacological Evaluation, and Molecular Modeling of Lappaconitine-1,5-Benzodiazepine Hybrids.

Diterpenoid alkaloids, originating from the amination of natural tetracyclic diterpenes, have long interested scientists due to their medicinal uses and infamous toxicity which has limited the clinical application of the native compound. Alkaloid lappaconitine extracted from various and species has displayed extensive bioactivities and active ongoing research to reduce its adverse effects. A convenient route to construct hybrid molecules containing diterpenoid alkaloid lappaconitine and 3-1,5-benzodiazepine fragments was proposed.

Investigation of 1,4-Substituted 1,2,3-Triazole Derivatives as Antiarrhythmics: Synthesis, Structure, and Properties.

Here, we investigated the reaction of 1,3-dipolar cycloaddition of 1,3-diazido-2-nitro-2- azapropane (DANP) to propargyl alcohol over a copper-based catalyst and identified the optimum reaction conditions that enable the synthesis of 2-nitro-1,3-bis(4,4'-dihydroxymethyl)-1,2,3-triazolyl-2-azapropane () in more than 84% yield. The reaction between DANP, 1,5-diazido-3-nitrazapentane, and phenylacetylene produced the respective 1,2,3-triazole derivatives in 83% and 71% yields, respectively. The structures of the resultant compounds were validated by infrared and NMR spectroscopies and elemental analysis.

Natural Products as a Source of Antiarrhythmic Drugs.

Throughout the development of medicine, the spotlight has been held by the search for new drugs blocking different types of arrhythmia. In the past decade, much attention was given to the selection of active antiarrhythmic substances from plant material. It has been shown that these compounds have a good antiarrhythmic effect, and their chemical modifications substantially increase their major effects while adding other beneficial pharmacological properties.

Lappaconitine: influence of halogen substituent on the antiarrhythmic activity.

The current paper presents research results related to antiarrhythmic activity of halogen-containing derivatives of lappaconitine. Lappaconitine derivatives with iodine, chlorine or bromine substituting the anthranilate moiety at C-5` position were shown in vivo and in vitro to exhibit a more (Br, I) or less (Cl) pronounced antiarrhythmic activity in the models of calcium chloride- and adrenaline-induced arrhythmias as compared with the reference compound lappaconitine. The intensity of antiarrhythmic action depending on halogen substituent was found to be expressed by the following order: Cl < I < Br.

Glycidipine, a promising hypotensive and cardioprotective agent.

Toxicological pharmacological study of the molecular complex of nifedipine and glycyrrhizic acid 1:10 (glycidipine) obtained using mechanochemical technique was carried out. High hypotensive and cardioprotective effects of the agent were demonstrated. Chronic administration (45 days) produced no toxic effects in vital organs and systems of Wistar rats and ISIAH rats.

[Improvement of the pharmacological activity of nifedipine by mechanochemical complexation with glycyrrhizic acid].

A new water-soluble form of the calcium blocker nifedipine (NF) with glycyrrhizic acid (GA) (with molecular ratio 1:4) has been obtained by mechanochemical synthesis. Its pharmacological advantages in comparison with nifedipine were determined. An effective dose of nifedipine in complex reduced to 10 times as compared to its therapeutic dose while high antihypertensive activity preservation and pleiotropic antiarhythmic activity enhancement.

The complexes of drugs with carbohydrate-containing plant metabolites as pharmacologically promising agents.

Complexation of known drugs with carbohydrate-containing plant metabolites is a promising way to synthesize new drugs that does not only save pharmacological properties of initial agent but also acquire a number of advantageous features such as increased water solubility, bioavailability and decreased toxicity. This review reports on the development and pharmacological evaluation of novel complexes of various well-known drugs with vegetable coplexation agents: glycyrrhizic acid, Stevia glycosides, gypsogenin tetraoside, pectin, xyloglucan, arabinogalactan. The aim of this review is to describe advantages of the new approach, suggested by authors, in the development of low toxic and high-performance drugs.

[Gender-related differences in EEG coherence in Stroop task].

Gender-related differences in EEE coherence were studied in young male and female university students during performance of Stroop task, in which color and word could be congruent or incongruent and spatially integrated or separated. The most clear-cut gender-related differences in the EEG coherence were revealed in the alpha2 and beta frequency bands. In the alpha2 band, gender-related differences in the interhemispheric coherence were associated with spatial characteristics of stimuli: left or right presentation and features of mutual localization of relevant and irrelevant stimuli.

Frequency-spatial organization of brain electrical activity in creative verbal thought: the role of the gender factor.

Gender-related differences in the EEG correlates of creative thought were studied by mapping EEG power during performance of a Remote Associations Task as compared with verbal word-generation and simple association tasks. Right-handed students (18 male, 21 female) took part in the studies. Gender-related differences were seen in the factor structure of measures of verbal activity and in the larger number of words generated for a given letter in women than in men.

Antiarrhythmic activity of 4,6-di(het)aryl-5-nitro-3,4-dihydropyrimidin-(1H)-2-ones and its effects on arterial pressure in rats.

The antiarrhythmic activity of 4,6-di(het)aryl-5-nitro-3,4-dihydropyrimidin-(1H)-2-ones toward two types of experimental rat arrhythmia has been studied. With CaCl(2) induced arrhythmia model, several agents have demonstrated high antiarrhythmic activity and the lack of influence on arterial pressure of rats.

[Antiarrhythmic activity of alaglyzin].

The activity of alaglyzin, a new drug based on a clathrate complex of allapinine (well-known antiarrhythmic) with glycyrrhizic acid (GA), was studied on the models of arrhythmia induced by itraperitoneal injections of calcium chloride (CaCl2) and adrenaline (epinephrine) in rats. Alaglyzin is less toxic than allapinine (LD50 70 and 6 mg/kg, respectively), and the effective dose of the parent compound in the complex form is also about 12 times lower than that in the reference drug. The experiments showed a dose dependent action of alaglyzin.

[Gender differences in EEG coherence during memorization of dichotically and monaurally presented verbal stimuli].

Gender differences in changes of coherence values in the theta and alpha frequency bands during encoding of dichotically and monaurally presented verbal information were studied. Right-handed students (14 male and 14 female subjects) participated in experiments. The EEG was recorded from 16 electrodes placed at homologous sites of the left and the right hemispheres.

[Sex differences in EEG power changes in retention of dichotically and monaurally presented verbal stimuli].

EEG power mapping was used to study gender differences in hemispheric functional organization during memorizing dichotically and monaurally presented verbal information. Right-handed students (12 men and 14 women) participated in experiments. The EEG was recorded from 16 electrodes placed at homologous sites of the left and right brain hemispheres.