New arylpiperazine derivatives with antidepressant-like activity containing isonicotinic and picolinic nuclei: evidence for serotonergic system involvement

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Pharmacological and Structure-Activity Relationship Evaluation of 4-aryl-1-Diphenylacetyl(thio)semicarbazides

This article describes the synthesis of six 4-aryl-(thio)semicarbazides (series a and b) linked with diphenylacetyl moiety along with their pharmacological evaluation on the central nervous system in mice and computational studies, including conformational analysis and electrostatic properties. All thiosemicarbazides (series b) were found to exhibit strong antinociceptive activity in the behavioural model. Among them, compound 1-diphenylacetyl-4-(4-methylphenyl)thiosemicarbazide 1b was found to be the most potentan algesic agent, whose activity is connected with the opioid system. For compounds from series a significant anti-serotonergic effect, especially for compound 1-diphenylacetyl-4- (4-methoxyphenyl)semicarbazide 2b was observed. The computational studies strongly support the obtained results

Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

Nitric oxide (NO) is a relatively novel messenger that plays a significant role in a wide range of physiological processes. Currently, it is known that, both, lack and excess of NO can cause diseases, thus a lot of substances have been discovered and utilized which can change the concentration of this molecule within the organism. The aim of the present work is to provide an overview of currently used agents modulating the L-arginine:NO:cGMP pathway, as well as to summarize current understanding of their pharmacological profiles. Nowadays, most of these agents are employed particularly in the treatment of cardiovascular diseases. Further studies can hold promise for enhancing the therapeutic equipment for a variety of other impairments, such as osteoporosis, and also in treatments of the central nervous system

ANTINOCICEPTIVE AND ANTIANXIETY ACTIVITY OF HYDROETHANOLIC EXTRACTS OF THREE IMPATIENS SPECIES IN MICE

The plants of the Impatiens L. (Balsaminaceae) have been used for a long time in folk medicine in different painful conditions, and to treat rheumatism, isthmus and crural aches, fractures, superficial infections, fingernail inflammation. This study was undertaken to determine the pharmacological profile of hydroethanolic extracts from Impatiens glandulifera, I. noli-tangere and I. parviflora. A range of behavioral assessments was applied to evaluate the effects of obtained extracts i.e. measurement of body temperature, tests of locomotor activity and motor coordination, nociceptive reaction and anxiety-like behavior. Hydroethanolic extracts were analyzed for total polyphenol (TPC), flavonoid (TFC), flavones/flavonols (TFFC), and flavonones/dihydroflavonols (TFDC) content. Our results show that the extracts from Impatiens species contain high levels of TPC, TFC, TFFC, and TFDC. Oral (i.e., by gavage) administration of Impatiens L. extracts (except for I. noli-tangere) presented an antinociceptive or/and anti-inflammatory activity in the writhing test. The antinociceptive effect of I. parviflora leaves (100 mg/kg) and I. glandulifera flowers (100 mg/kg) was reversed by naloxone. I. glandulifera flowers and roots extracts (100 mg/kg) increased the reaction time to the thermal stimulus in the hot-plate test. All extracts from I. glandulifera (100 mg/kg) showed antianxiety effect in the elevated plus-maze test. It is worth noting that none of the extracts, at the highest used dose – 0.1 ED50 (200 mg/kg), caused coordination impairments or myorelaxation as measured in the rota-rod and chimney tests. These results seem to suggest that the tested extracts are not neurotoxic

New Atypical Antipsychotics in the Treatment of Schizophrenia and Depression

Schizophrenia and depression are heterogeneous disorders. The complex pathomechanism of the diseases imply that medication responses vary across patients. Many psychotropic drugs are available but achieving optimal therapeutic effect can be challenging. The evidence correlates well with clinical observations, suggesting that new atypical antipsychotic drugs are effective against negative and cognitive symptoms of schizophrenia, as well as against affective symptoms observed in depression. The purpose of this review presents the background and evidence for the use of the new second/third-generation antipsychotics (aripiprazole, cariprazine, lurasidone, asenapine, brexpiprazole, lumateperone, pimavanserin) in treatment of schizophrenia and depression. We have first provided a brief overview of the major neurobiological underpinnings of schizophrenia and depression. We then shortly discuss efficacy, safety and limitations of ongoing pharmacotherapy used in depression and schizophrenia. Mainly, we have focused this review on the therapeutic potential of new atypical antipsychotic drugs—currently existing—to be effective in psychotic, as well as in affective disorders

Currently used anorexic drugs in the pharmacotherapy of obesity

W przedstawionej pracy dokonano przeglądu leków anorektycznych działających ośrodkowo poprzez hamowanie uczucia głodu i wykorzystywanych do farmakologicznego leczenia otyłości. Omówiono problem otyłości jako choroby cywilizacyjnej, która dotyka coraz więcej osób na świecie. Opisano prawdopodobne przyczyny takiego stanu rzeczy, skutki zdrowotne oraz wskazania do farmakoterapii ze zwróceniem szczególnej uwagi na mechanizm odczuwania głodu i sytości. Zaprezentowano preparaty dostępne zarówno na terenie Stanów Zjednoczonych, jak i w Unii Europejskiej. Skupiono się na przybliżeniu mechanizmów ich działania, skutków ubocznych, oraz efektach terapeutycznych uzyskanych z przeprowadzonych badań. Uwzględniono również leki stosowane w przeszłości, wyjaśniając dlaczego zostały wycofane z obrotu.The presented study reviews the possibilities of pharmacological obesity treatment through the use of anorectic drugs - acting on the central nervous system by reducing appetite. The problem of obesity as a civilization disease that affects more and more people in the world was discussed. The likely causes of such a state of affairs, health effects and indications for pharmacotherapy have been described, paying particular attention to the mechanism of feeling hungry and satiety. Preparations available both in the United States and in the European Union were presented. The focus was on the mechanism of their action, therapeutic effects resulting from the research and side effects. Medicines used in the past are also included, explaining why they were withdrawn from the market

New Drugs - From Necessity to Delivery

How to get a new drug to market? How much time does it take to go from the idea to implementation? In this study we followed the path drugs take from synthesis to introduction to the market. In doing so, articles in the PubMed and the Google Scholar database have been analyzed using the keywords: drug development, drug design, lead compound, preclinical trials, clinical trials. The available literature was subjectively selected due to its usefulness in the topic. Based on the obtained articles, we presented the stages that a would-be drug takes on the way from the idea to marketing. Herein, it is underlined that the process of creating new drugs is long, extremely labor-intensive, and involves many restrictions in the context of the use of animals, as well as human

Synthesis and Pharmacological Evaluation of Novel 1-(1,4-Alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted Urea Derivatives

Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a–m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a–c and appropriate isocyanates 2 in dichloromethane. The compounds were subjected to in silico ADMET studies in order to select best candidates for in vivo experiments. The effects of the compounds on the spontaneous locomotor activity and amphetamine-evoked hyperactivity were estimated. Analgesic activity, without or in the presence of naloxone, was assessed in the writhing test. The tendency to change the HTR, evoked by l-5-HTP and the involvement in alteration in body temperature in mice was studied. Additionally, to check possible occurrence of drug-induced changes in the muscle relaxant activity of mice, which may have contributed to their behaviour in other tests, the rota-rod and chimney tests were performed. The new urea derivatives exerted significant activities in the performed pharmacological tests, although the presented results show a preliminary estimation, and thus, need to be extended for identification and understanding the complete pharmacological profile of the examined compounds