The antidepressant-like activity of chiral xanthone derivatives may be mediated by 5-HT1A receptor and β-arrestin signalling.

Background: Our previous studies showed that xanthone derivatives with -(2-methoxyphenyl)piperazine fragment have an affinity to the 5-HT1A receptor and show antidepressant-like properties in rodents. In this study, we tested three xanthone derivatives, HBK-1 and its enantiomers, in which we increased the distance between the piperazine and xanthone fragments by using a hydroxypropoxy linker. We hypothesized that this would increase the binding to the 5-HT1A receptor and consequently, pharmacological activity.

Synthesis and Pharmacological Evaluation of Novel Silodosin-Based Arylsulfonamide Derivatives as α/α-Adrenergic Receptor Antagonist with Potential Uroselective Profile.

Benign prostatic hyperplasia (BPH) is the most common male clinical problem impacting the quality of life of older men. Clinical studies have indicated that the inhibition of α-/α adrenoceptors might offer effective therapy in lower urinary tract symptoms. Herein, a limited series of arylsulfonamide derivatives of (aryloxy)ethyl alicyclic amines was designed, synthesized, and biologically evaluated as potent α₁-adrenoceptor antagonists with uroselective profile.

Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.

Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62).

INACTIVATION OF ALDEHYDE DEHYDROGENASE BY NITROGLYCERIN IN THE PRESENCE AND ABSENCE OF LIPOIC ACID AND DIHYDROLIPOIC ACID. IMPLICATIONS FOR THE PROBLEM OF DIFFERENTIAL EFFECTS OF LIPOIC ACID IN VITRO AND IN VIVO.

Lipoic acid (LA-(SS), LA) and its reduced form - dihydrolipoic acid DHLA-(SH)2, DHLA) are synthesized mainly in the mammalian liver. In this study, we investigated in viti the inactivation of yeast aldehyde dehydrogenase (ALDH) by nitroglycerin (GTN) in the presence and absence of LA and DHLA. In vivo studies were performed to answer the question whether LA administered jointly with GTN for 8 days will affect the ALDH activity in the rat liver.

Arylsulfonamide derivatives of (aryloxy)ethyl pyrrolidines and piperidines as α-adrenergic receptor antagonist with uro-selective activity.

A series of arylsulfonamide derivatives of (aryloxy)ethyl pyrrolidines and piperidines was synthesized to develop new α-adrenoceptor antagonists with uroselective profile. Biological evaluation for α- and α-adrenorecepor showed that tested compounds 13-37 displayed high-to-moderate affinity for the α-adrenoceptor (K=34-348nM) and moderate selectivity over α-receptor subtype. Compounds with highest affinity and selectivity for α-adrenoceptor were evaluated in vitro for their intrinsic activity toward α- and α-adrenoceptor subtypes.

Pyrrolidin-2-one derivatives may reduce body weight in rats with diet-induced obesity.

Unlabelled: Obesity affects an increasing number of individuals in the human population and significant importance is attached to research leading to the discovery of drug which would effectively reduce weight. The search for new drugs with anorectic activity and acting within the adrenergic system has attracted the interest of researchers. This study concerns the experimental effects on body weight of α2-adrenoceptor antagonists from the group of pyrrolidin-2-one derivatives in rats with diet-induced obesity.

Antidepressant-like activity of aroxyalkyl derivatives of 2-methoxyphenylpiperazine and evidence for the involvement of serotonin receptor subtypes in their mechanism of action.

Since serotonin (5-HT) is strongly involved in the etiology and pathophysiology of depression, the development of new antidepressants is still based on the serotonergic system. The complexity of serotonergic system provides an opportunity for the development of compounds with multiple and complementary mechanism of action. This study describes serotonin receptor profile, functional characterization, and pharmacological in vivo evaluation of new aroxyalkyl derivatives of 2-methoxyphenylpiperazine.

Antiarrhythmic and α-Adrenoceptor Antagonistic Properties of Novel Arylpiperazine Derivatives of Pyrrolidin-2-one.

In an effort to develop α-adrenoceptor antagonists with antiarrhythmic activity, we designed a series of pyrrolidin-2-one derivatives. The α1- and α2-adrenorecepor affinities of the new pyrrolidin-2-one derivatives were determined using a radioligand binding assay. The most active compound was then tested in vitro for intrinsic activity toward α(1A)- and α(1B)-adrenoceptors and in vitro for antiarrhythmic activity in epinephrine-induced arrhythmia in rats.

A Comparison of the Anorectic Effect and Safety of the Alpha2-Adrenoceptor Ligands Guanfacine and Yohimbine in Rats with Diet-Induced Obesity.

The search for drugs with anorectic activity, acting within the adrenergic system has attracted the interest of researchers. Partial α2-adrenoceptor agonists might offer the potential for effective and safe treatment of obesity. We compared the effectiveness and safety of α2-adrenoceptor ligands in reducing body mass.

Antiarrhythmic activity in occlusion-reperfusion model of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino} propan-2-ol and its enantiomers.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide, especially in developed countries. The most serious problem after myocardial infarction is reperfusion injury that manifests as functional impairment, arrhythmia, and accelerated progression of cell death in certain critically injured myocytes. Subsequently the infarcted myocardium develops features of necrosis and reactive inflammation.

The influence of the route of administration of gold nanoparticles on their tissue distribution and basic biochemical parameters: In vivo studies.

Background: The gold nanoparticles (AuNP's) exhibit interesting chemical and physical properties and for this reason are intensively tested in medicine. However there is a lack of information about toxicity of those nanoparticles as well as their excretion from the body. Thus, the aim of the present study was to investigate the influence of the route of administration of gold nanoparticles to rats on their distribution in tissues and excretion rate.

α-Adrenoceptor antagonistic and hypotensive properties of novel arylpiperazine derivatives of pyrrolidin-2-one.

This study focused on a series of pyrrolidin-2-one derivatives connected via two or four methylene units to arylpiperazine fragment. The compounds obtained for α₁- and α₂-adrenoceptors were assessed. The compound with highest affinity for the α₁-adrenoceptors was 1-{4-[4-(2-chloro-phenyl)-piperazin-1-yl]-butyl}-pyrrolidin-2-one (10 h) with pKi=7.

Biofunctional studies of new 2-methoxyphenylpiperazine xanthone derivatives with α₁-adrenolytic properties.

Background: The aim of this study was to assess the selectivity of the studied xanthone derivatives for α1-adrenoceptor subtypes (α1A, α1B, α1D, α1L) in functional experiments in order to verify if they possess any selectivity for a distinct subtype of α1-adrenoceptor. Moreover, several pharmacological tests were carried out to assess whether they reveal other than α1-adrenoceptor blocking properties such as: antagonistic for 5-HT2 receptors, vasorelaxant or spasmolytic.

Methods: The influence on α1A-adrenoceptors was examined in biofunctional studies employing isolated rat vas deferens, on α1B-adrenoceptors in guinea-pig spleen, on α1D-adrenoceptors in rat aorta, and on α1L-adrenoceptors in rabbit spleen.

Alpha lipoic acid protects the heart against myocardial post ischemia-reperfusion arrhythmias via KATP channel activation in isolated rat hearts.

The cardiovascular effects of alpha lipoic acid were evaluated in isolated rat hearts exposed to ischemia-reperfusion injury in vitro. Alpha-lipoic acid raised the level of sulfane sulfur playing an important role in the release of hydrogen sulfide. H2S was shown to prevent the post-reperfusion arrhythmias and to protect the cardiomyocytes from death caused by hypoxia.

Antiarrhythmic and hypotensive activities of 1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-pyrrolidin-2-one (MG-1(R,S)) and its enantiomers.

The compound MG-1(R,S), (1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl]-pyrrolidin-2-one, and its enantiomers were tested for electrocardiographic, antiarrhythmic and hypotensive activities. The racemic mixture (MG-1(R,S)) and its S-enantiomer significantly decreased systolic and diastolic blood pressure and possessed antiarrhythmic activity. The S-enantiomer displayed the greatest effect.