Synthesis and biological investigation of new equatorial (ß) stereoisomers of 3-aminotropane arylamides with atypical antipsychotic profile.

A series of novel 3ß-aminotropane derivatives containing a 2-naphthalene or a 2-quinoline moiety was synthesised and evaluated for their affinity for 5-HT1A, 5-HT2A and D2 receptors. Their affinity for the receptors was in the nanomolar to micromolar range. p-Substitution (6c, 6f, 6i, 6l, 6o), as well as substitution with chlorine atoms (6g, 6h, 6i), led to a significant increase in binding affinity for D2 receptors with compounds 6f (Ki=0.6nM), 6c and 6i (Ki=0.4nM), having the highest binding affinities. m-Substituted derivatives were the most promising ligands in terms of 5-HT2A receptor binding affinity whereas 2-quinoline derivatives (10a, 10b) displayed the highest affinity for 5-HT1AR and were the most selective ligands with Ki=62.7nM and Ki=30.5nM, respectively. Finally, the selected ligands 6b, 6d, 6e, 6g, 6h, 6k, 6n and 6o, with triple binding activity for the D2, 5-HT1A and 5-HT2A receptors, were subjected to in vivo tests, such as those for induced hypothermia, climbing behaviour and the head twitch response, in order to determine their pharmacological profile. The tested ligands presented neither agonist nor antagonist properties for the 5-HT1A receptors in the induced hypothermia and lower lip retraction (LLR) tests. All tested compounds displayed antagonistic activity against 5-HT2A, with 6n and 6o being the most active. Four (6b, 6k, 6n and 6o) out of eight tested compounds could be classified as D2 antagonists. Additionally, evaluation of metabolic stability was performed for selected ligands, and introduction of halogen atoms into the benzene ring of 6h, 6k, 6n and 6o improved their metabolic stability. The project resulted in the selection of the lead compounds 6n and 6o, which had antipsychotic profiles, combining dopamine D2-receptor and 5-HT2A antagonism and metabolic stability.

Social media literacy among nursing students during the COVID-19 pandemic - does year of study matter? A nationwide cross-sectional study.

INTRODUCTION AND OBJECTIVE: Research to date indicates that student competencies in various dimensions of social media use vary depending on, for example, the field of study or stage of education. The aim of the study was assessment of social media literacy in a group of undergraduate nursing students, based on the year of study. MATERIAL AND METHODS: Respondents: 679 nursing students from 11 Polish medical universities who began or continued their education during the COVID-19 pandemic. First-year students (N = 397, 58.73%) and women (N = 589, 87.13%) constituted the largest group. The Perceived Social Media Literacy Scale was used. Statistical analysis used the Kruskal-Wallis one-way analysis-of-variance-by-ranks to analyse differences in PSML scores, and Dunn's test to analyse differences in PSML scores between individual years of study (α= 0.05). RESULTS: The level of social media literacy between students differed significantly (p < 0.001). Students rated their technical competency the highest (H = 29.722, p < 0.001), social relationships (H = 20.946, p < 0.001) and informational awareness (H = 21.054, p < 0.001) the lowest. The lowest scores in the self-assessment of social media literacy were noted among first-year students (M = 55.85, Max = 70.0; p < 0.001), and the highest among second-year students (M = 60.99, Max = 70.0; p < 0.001). CONCLUSIONS: Nursing students rated their competency lowest in the sphere related to verifying the content of messages appearing on social media, which may have a significant impact on their professional competencies. Differences in the level of social media literacy among students of different years of study should be taken into account when designing training in this field.

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with Hybrid Structure as a Candidate for a Broad-Spectrum Antiepileptic Drug.

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZ-induced seizures in mice. Thus, AS-1 may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 µM, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 µM).