Amide Research Articles

Determination of Erucamide Slip Additive in Polypropylene Masterbatch: Comparison of Soxhlet and Dissolution-Precipitation Method

Erucamide is a long-chain carboxylic acid amide used as a slip agent in plastic films. In this research, the slip additive in polypropylene masterbatch with 6% erucamide content was extracted by comparing two methods which are dissolution-precipitation and the Soxhlet method. The variant of sonication times in the dissolution-precipitation method and extractor-solvents in the Soxhlet method were done to determine the optimum parameter in each method. The examination of slip additive content in each extraction method used the KBr Disk-FTIR and the weight loss of sample analysis. The form of the sample, which was in the granule and powder form was also studied. Based on the result, the dissolution-precipitation method with 3 minutes of sonication times and the use of ethyl acetate as extractor solvent in the Soxhlet method gave a closer result for additive content in the masterbatch. The powder form of the sample also gave better results than the granule form for the extraction of erucamide. The Soxhlet method in the powder form showed comparable results with the dissolution-precipitation method by KBr Disk-FTIR analysis and higher results by weight loss analysis. By comparing the two methods of extraction, the Soxhlet method showed more robustness and efficiency for extraction of erucamide additive in polypropylene masterbatch than the dissolution-precipitation method.

Identification and Characterization of a Bacterial Periplasmic Solute Binding Protein That Binds l-Amino Acid Amides.

Periplasmic solute-binding proteins (SBPs) are key ligand recognition components of bacterial ATP-binding cassette (ABC) transporters that allow bacteria to import nutrients and metabolic precursors from the environment. Periplasmic SBPs comprise a large and diverse family of proteins, of which only a small number have been empirically characterized. In this work, we identify a set of 610 unique uncharacterized proteins within the SBP_bac_5 family that are found in conserved operons comprising genes encoding (i) ABC transport systems and (ii) putative amidases from the FmdA_AmdA family. From these uncharacterized SBP_bac_5 proteins, we characterize a representative periplasmic SBP from Mesorhizobium sp. A09 (MeAmi_SBP) and show that MeAmi_SBP binds l-amino acid amides but not the corresponding l-amino acids. An X-ray crystal structure of MeAmi_SBP bound to l-serinamide highlights the residues that impart distinct specificity for l-amino acid amides and reveals a structural Ca2+ binding site within one of the lobes of the protein. We show that the residues involved in ligand and Ca2+ binding are conserved among the 610 SBPs from experimentally uncharacterized FmdA_AmdA amidase-associated ABC transporter systems, suggesting these homologous systems are also likely to be involved in the sensing, uptake, and metabolism of l-amino acid amides across many Gram-negative nitrogen-fixing soil bacteria. We propose that MeAmi_SBP is involved in the uptake of such solutes to supplement pathways such as the citric acid cycle and the glutamine synthetase-glutamate synthase pathway. This work expands our currently limited understanding of microbial interactions with l-amino acid amides and bacterial nitrogen utilization.

Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide.

Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn's disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.

Sixty years of recurrence prevention in mood disorders.

This year, we observe sixty's anniversary of the article by a British psychiatrist, Geoffrey Hartigan, demonstrating, for the first time, the possibility of preventing of the recurrence of mood disorders by using lithium salts. Herein, a history of prevention of recurrences of mood disorders both worldwide and in Poland will be presented concerning both lithium and other mood-stabilizing drugs. The merit for verifying the prophylactic lithium effect in the 1960-1970s should be given to Danish researchers, Mogens Schou and Poul Baastrup. In Poland, the first paper on prophylactic lithium appeared already in 1971. In the 1970s, French researchers showed prophylactic activity of valproic acid amide, and Japanese researchers - carbamazepine. In the 1980th, studies on valproic acid amide were performed in the 2nd Psychiatric Clinic of the Institute of Psychiatry and Neurology led by Prof. Pużyński. Since the mid-1990s, 2nd generation of mood-stabilizing drugs has been introduced, including some atypical antipsychotics (clozapine, olanzapine, quetiapine, aripiprazole, risperidone) and anticonvulsant drug, lamotrigine, showing prophylactic activity in bipolar mood disorder. The studies on lithium resulted in the identification of factors connected with its prophylactic efficacy as well as the antisuicidal, antiviral, and neuroprotective effects of this drug. From a sixty-year perspective following Hartigan's article, it seems that his pioneering concept on the possibility of pharmacological influence on the course of mood disorders was fully confirmed. Current Polish recommendations on pharmacological prophylaxis of mood disorders were presented in the books "Standardy leczenia niektórych zaburzeń psychicznych" and "Psychofarmakologia kliniczna", both published in 2022.

Unraveling the molecular basis of cannabidiolic acid methyl Ester's anti-depressive effects in a rat model of treatment-resistant depression

Major depressive disorder (MDD) stands as a significant cause of disability globally. Cannabidiolic Acid-Methyl Ester (CBDA-ME) (EPM-301, HU-580), a derivative of Cannabidiol, demonstrates immediate antidepressant-like effects, yet it has undergone only minimal evaluation in psychopharmacology. Our goal was to investigate the behavioral and potential molecular mechanisms associated with the chronic oral administration of this compound in the Wistar Kyoto (WKY) genetic model of treatment-resistant depression. Male WKY rats were subjected to behavioral assessments before and after receiving chronic (14-day) oral doses of CBDA-ME (0.5 mg/kg), 15 mg/kg of imipramine or vehicle. At the end of the study, plasma corticosterone levels and mRNA expression of various genes in the medial Prefrontal Cortex and Hippocampus were measured. Behavioral outcomes from CBDA-ME treatment indicated an antidepressant-like effect similar to imipramine, as oral ingestion reduced immobility and increased swimming duration in the Forced Swim Test. Neither treatment influenced locomotion in the Open Field Test nor preference in the Saccharin Preference Test. The behavioral impact in WKY rats coincided with reduced corticosterone serum levels, upregulated mRNA expression of Cannabinoid receptor 1, Fatty Acid Amide Hydrolase, and Corticotropin-Releasing Hormone Receptor 1, alongside downregulation of the Serotonin Transporter in the hippocampus. Additionally, there was an upregulation of CB1 mRNA expression and downregulation of Brain-Derived Neurotrophic Factor in the mPFC. These findings contribute to our limited understanding of the antidepressant effects of CBDA-ME and shed light on its potential psychopharmacological mechanisms. This discovery opens up possibilities for utilizing cannabinoids in the treatment of major depressive disorder and related conditions.

Exploring the Hypocholesterolemic Potential of a Fucus vesiculosus Extract: Omic Insights into Molecular Mechanisms at the Intestinal Level.

High blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells' metabolites and proteins was analysed to gain a deeper understanding of its mode of action on lipids' metabolism, particularly concerning the absorption and transport of exogenous cholesterol. Caco-2 cells, differentiated into enterocytes, were exposed to the extract, and analysed by untargeted metabolomics and proteomics. The results of the metabolomic analysis showed statistically significant differences in glutathione content of cells exposed to the extract compared to control cells, along with an increased expression of fatty acid amides in exposed cells. A proteomic analysis showed an increased expression in cells exposed to the extract compared to control cells of FAB1 and NPC1, proteins known to be involved in lipid metabolism and transport. To the extent of our knowledge, this study is the first use of untargeted metabolomics and a proteomic analysis to investigate the effects of F. vesiculosus on differentiated Caco-2 cells, offering insights into the molecular mechanism of the extract's compounds on intestinal cells.

Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

Development of the Squaramide Scaffold for High Potential and Multielectron Catholytes for Use in Redox Flow Batteries.

Nonaqueous organic redox flow batteries (N-ORFBs) are a promising technology for grid-scale storage of energy generated from intermittent renewable sources. Their primary benefit over traditional aqueous RFBs is the wide electrochemical stability window of organic solvents, but the design of catholyte materials, which can exploit the upper range of this window, has proven challenging. We report herein a new class of N-ORFB catholytes in the form of squaric acid quinoxaline (SQX) and squaric acid amide (SQA) materials. Mechanistic investigation of decomposition in battery-relevant conditions via NMR, HRMS, and electrochemical methods enabled a rational design approach to optimizing these scaffolds. Three lead compounds were developed: a highly stable one-electron SQX material with an oxidation potential of 0.51 V vs Fc/Fc+ that maintained 99% of peak capacity after 102 cycles (51 h) when incorporated into a 1.58 V flow battery; a high-potential one-electron SQA material with an oxidation potential of 0.81 V vs Fc/Fc+ that demonstrated negligible loss of redox active material as measured by pre- and postcycling CV peak currents when incorporated in a 1.63 V flow battery for 110 cycles over 29 h; and a proof-of-concept two-electron SQA catholyte material with oxidation potentials of 0.48 and 0.85 V vs Fc/Fc+ that demonstrated a capacity fade of just 0.56% per hour during static H-cell cycling. These findings expand the previously reported space of high-potential catholyte materials and showcase the power of mechanistically informed synthetic design for N-ORFB materials development.

Measurement report: Characteristics of nitrogen-containing organics in PM2.5 in Ürümqi, northwestern China – differential impacts of combustion of fresh and aged biomass materials

Abstract. Nitrogen-containing organic compounds (NOCs) are abundant and important aerosol components deeply involved in the global nitrogen cycle. However, the sources and formation processes of NOCs remain largely unknown, particularly in the city (Ürümqi, China) farthest from the ocean worldwide. Here, NOCs in PM2.5 collected in Ürümqi over a 1-year period were characterized by ultra-high-resolution mass spectrometry. The abundance of CHON compounds (mainly oxygen-poor unsaturated aliphatic-like species) in the positive ion mode was higher in the warm period than in the cold period, which was largely attributed to the contribution of fresh biomass material combustion (e.g., forest fires) associated with amidation of unsaturated fatty acids in the warm period, rather than the oxidation processes. However, CHON compounds (mainly nitro-aromatic species) in the negative ion mode increased significantly in the cold period, which was tightly related to aged biomass combustion (e.g., dry straws) in wintertime Ürümqi. For CHN compounds, alkyl nitriles and aromatic species showed higher abundance in the warm and cold periods, respectively. Alkyl nitriles can be derived from fresh biomass material combustion associated with the dehydration of amides (the main CHON compounds in the warm period). In contrast, aromatic species were tightly related to aged biomass burning. These findings further suggested different impacts of the combustion of fresh and aged biomass materials on NOC compositions in different seasons. The overall results shed light on the mechanisms by which fresh and aged biomass materials release different NOCs during combustion.

Interaction of melanoidins, proline, and valine with sorbents of various nature

The isolation of pure amino acids from industrial solutions is one of the important tasks of production. Solutions of amino acids obtained as a result of chemical or microbiological treatment contain a number of impurities, mostly organic ones. The microbiological synthesis of proline is accompanied by the presence of valine, leucine, alanine, and coloured high-molecular components in the culture liquid that belong to the melanoidin group. Melanoidins of proline acid production are high-molecular compounds containing amino acid fragments, heterocyclic structures, and amide bonds. Melanoidins in solutions can exist in cationic, bipolar, and anionic forms. They have different molecular weights, molecular sizes, and isoelectric states. Various ion exchange methods can be used to isolate the target amino acid. It should be noted that the interaction of amino acids with ion-exchange materials is a complex process depending on the electrolytic properties of the sorbate and sorbent and accompanied by multiple side effects. It is necessary to know the specific features of interaction in the “amino acid - sorbent” system and the factors that affect the transport of sorbate ions in the sorbent phase when choosing an isolation method for the target product. The goal of this work was to determine the impact of pH on the sorption process of proline and valine by high-basic ion exchangers, to identify the features of their interactions, and to use the obtained results to optimise the conditions for the separation of amino acids. We studied the process of interaction of bipolar ions and anions of proline (Pro±, Pro-) and valine (Val±, Val-) with anionites AV-17-8 and AV-17-2P. It was established that the mechanism of amino acid ion exchange in granular sorbents depended on the рН value in the “anionite - external solution” system. Based on the studied interactions, we suggested the methods of the anion-exchange separation of proline and valine. The selected conditions of separation of proline and valine were on anionite AV-17-2P in ОН-form (рН of the initial solution was 6.6-6.7; the solution flow rate was 2 cm3/min). The results of separation of proline and valine indicated that even in a one-step sorption process, five to seven fractions with proline contained no valine ions, while the concentration of proline was 2.0-2.7 times higher as compared to the original solution.

Long-term use of etomidate disrupts the intestinal homeostasis and nervous system in mice

Etomidate (ETO) is used as an anesthetic in surgery, but it is being abused in some populations. The damage caused by long-term intake of ETO to intestinal and brain functions is not yet clear, and it remains to be determined whether the drug affects the central nervous system through the gut-brain axis. This study aimed to investigate the neurotoxic and gastrointestinal effects of ETO at doses of 1 mg/kg and 3 mg/kg in mice over 14 consecutive days. The results showed that long-term injection of ETO led to drug resistance in mice, affecting their innate preference for darkness and possibly inducing dependence on ETO. The levels of 5-hydroxytryptamine in the brain, serum, and colon decreased by 37%, 51%, and 42% respectively, while the levels of γ-aminobutyric acid reduced by 38%, 52%, and 41% respectively. H&E staining revealed that ETO reduced goblet cells in the colon and damaged the intestinal barrier. The expression of tight junction-related genes Claudin4 and ZO-1 was downregulated. The intestinal flora changed, the abundance of Akkermansia and Lactobacillus decreased by 33% and 14%, respectively, while Klebsiella increased by 18%. TUNEL results showed that high-dose ETO increased apoptotic cells in the brain. The expression of Claudin1 in the brain was downregulated. Untargeted metabolomics analysis of the colon and brain indicated that ETO caused abnormalities in glycerophospholipid metabolism. Abnormal lipid metabolism might lead to the production or accumulation of lipotoxic metabolites, causing central nervous system diseases. ETO induced changes in the intestinal flora and metabolism, further affecting the central nervous system through the gut-brain axis. The study unveiled the detrimental effects on the brain and gastrointestinal system resulting from long-term intake of ETO, which holds significant implications for comprehending the adverse impact of ETO abuse on human health.

Clovamide and Its Derivatives-Bioactive Components of Theobroma cacao and Other Plants in the Context of Human Health.

Clovamide (N-caffeoyl-L-3,4-dihydroxyphenylalanine, N-caffeoyldopamine, N-caffeoyl-L-DOPA) is a derivative of caffeic acid, belonging to phenolamides (hydroxycinnamic acid amides). Despite a growing interest in the biological activity of natural polyphenolic substances, studies on the properties of clovamide and related compounds, their significance as bioactive components of the diet, as well as their effects on human health are a relatively new research trend. On the other hand, in vitro and in vivo evidence indicates the considerable potential of these substances in the context of maintaining human health or using them as pharmacophores. The name "clovamide" directly derives from red clover (Trifolium pratense L.), being the first identified source of this compound. In the human diet, clovamides are mainly present in chocolate and other cocoa-containing products. Furthermore, their occurrence in some medicinal plants has also been confirmed. The literature reports deal with the antioxidant, anti-inflammatory, neuroprotective, antiplatelet/antithrombotic and anticancer properties of clovamide-type compounds. This narrative review summarizes the available data on the biological activity of clovamides and their potential health-supporting properties, including prospects for the use of these compounds for therapeutic purposes.

Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors

Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-Δexon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism. CBD rescued the cognitive deficits displayed by juvenile Fmr1-Δexon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-Δexon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH. These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.

Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer's Disease.

Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aβ) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aβ-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.

Plant-Derived Caffeic Acid and Its Derivatives: An Overview of Their NMR Data and Biosynthetic Pathways.

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.

Sensitivity of Plasmopara viticola to selected fungicide groups and the occurrence of the G143A mutant in Australian grapevine isolates.

Grapevine downy mildew, caused by Plasmopara viticola, is an economically important disease in Australia and worldwide. The application of fungicides is the main tool to control this disease. Frequent fungicide applications can lead to the selection of resistant P. viticola populations, which has negative impacts on the management of the disease. Identification of resistance and its prevalence is necessary to inform resistance management strategies. A total of 86 P. viticola isolates were collected between 2017 and 2022 from vineyards in 15 growing regions across Australia for four fungicide groups; phenylamide (PA, group 4), carboxylic acid amide (CAA, group 40), quinone outside inhibitor (QoI, group 11) and quinone outside inhibitor stigmatellin binding type (QoSI, group 45). Decreased phenotypic sensitivity was detected for all four groups, and resistance to metalaxyl-M (PA) and pyraclostrobin (QoI), was detected. Genetic analysis to detect the G143A (QoI) and G1105S (CAA) mutations using amplicon-based sequencing was performed for 239 and 65 isolates collected in 2014-2017 and 2017-2022, respectively. G143A was detected in 8% and 52% of isolates, respectively, with strong association to phenotypic resistance. However, G1105S was not detected in any isolates. Plasmopara viticola isolates in Australia with resistance to at least two fungicide groups have been detected, therefore it is necessary to adopt resistance management strategies where resistance has been detected. Vineyards should continue to be monitored to improve management strategies for downy mildew. © 2024 Society of Chemical Industry.

Fatty acid amides of plant origin in elastomeric compositions

One of the strategic directions of chemical technology eco-modernization is the use of renewable natural raw materials to create ingredients for elastomeric composites. The use of fatty acids amides of sunflower oil, such as monoethanolamide and diethanolamide of sunflower oil fatty acids, and oleic acid amide, has been proposed for the rubber industry; their main characteristics have been determined. The effectiveness of the action of fatty acid amides in sulfur vulcanization system has been studied in unfilled and filled elastomeric composites of a model type based on butadiene--methylstyrene rubber with the presence of the investigated substances at a dosage of 1.5 phr per 100.0 phr of the rubber base. Using the rheometry method, it has been shown that the investigated fatty acid amides significantly activate and deepen the degree of sulfur vulcanization, and their activity in the composition of accelerated sulfur vulcanization activators depends on the structure. Fatty acid diethanolamide with a tertiary nitrogen atom exhibited the maximum activity. A positive effect of fatty acid amides on the gain coefficient, complex dynamic modulus, and mechanical loss tangent of rubber has been established.

Investigating LSA - a ‘legal high’ analogue to LSD, frequently used in the digital realm with relatively unknown effects

IntroductionPsychedelics are substances consumed for recreational use, the majority of these psychoactive substances are illegal and hard to obtain. Therefore, there is a demand for psychedelics legal and easier to access, these types of drugs are called ‘legal highs’. LSA (lysergic acid amide) is one of these new psychoactive substances, this drug is searched because it is known to have an effect similar to LSD. LSA has negative effects on body functioning not fully understood by the medical field.ObjectivesThis project aims to conduct a systematic review of the scientific health literature on LSA.Methods The following information was included in this review: articles reporting original data on physical effects, neurobiological effects, various bodily symptoms, social and cultural aspects in humans related to LSA, published in English, Portuguese, Spanish, Italian, and French. Studies involving animals, in vitro research, botanical studies, and non-original research were excluded. The following keywords were searched in the PubMed, Google Scholar, and Web of Science databases: (ergine or d-lysergic acid amide or LSA or d-lysergamide or lysergic acid amide). This study followed the PRISMA statement for systematic reviews and PRISMA checklist. The resulting data were tabulated and analyzed according to relevance.ResultsLSA, also known as ergine, is an ergot alkaloid with a chemical formula very similar to LSD. Ergine is found in plants of the Convolvulaceae family and is primarily consumed through chewing the seeds of these plants, soaking them in alcohol, or preparing an extract. The amount of LSA in each seed is inconsistent, making it unpredictable how much will be consumed, and these seeds may contain other harmful compounds. LSA is a partial agonist and antagonist of serotonergic receptors, with a preference for 5-HT1A and 5-HT2, and stimulation of D2 is related to nausea. It can cause symptoms including euphoria, hallucinations, anxiety, nausea, weakness, fatigue, tremors, and elevated blood pressure. In some cases, the use of LSA is associated with the use of other drugs, and there are case reports of LSA-induced PRES (Posterior Reversible Encephalopathy Syndrome), post-use suicides and the need for hospitalization due to psychosis-like states.Studies conducted on the quality of information about LSA on digital platforms indicate misinformation with incorrect data that can be harmful to those who ingest the drug. Additionally, there are studies suggesting that LSA may improve symptoms of cluster headaches.ConclusionsLSA is a legal drug in most countries, with widespread misinformation on the internet and limited control over its use. There are potential serious adverse effects caused by the drug, and it is often associated with other psychoactive substances. Greater knowledge about the drug is needed for diagnosing its use and abuse, as well as for educating the public.Disclosure of InterestNone Declared

Indirect and direct cannabinoid agonists differentially affect mesolimbic dopamine release and related behaviors.

The cannabinoid system is being researched as a potential pharmaceutical target for a multitude of disorders. The present study examined the effect of indirect and direct cannabinoid agonists on mesolimbic dopamine release and related behaviors in C57BL/6J (B6) mice. The indirect cannabinoid agonist N-arachidonoyl serotonin (AA-5-HT) indirectly agonizes the cannabinoid system by preventing the metabolism of endocannabinoids through fatty acid amide hydrolase inhibition while also inhibiting transient receptor potential vanilloid Type 1 channels. Effects of AA-5-HT were compared with the direct cannabinoid receptor Type 1 agonist arachidonoyl-2'-chloroethylamide (ACEA). In Experiment 1, mice were pretreated with seven daily injections of AA-5-HT, ACEA, or vehicle prior to assessments of locomotor activity using open field (OF) testing and phasic dopamine release using in vivo fixed potential amperometry. Chronic exposure to AA-5-HT did not alter locomotor activity or mesolimbic dopamine functioning. Chronic exposure to ACEA decreased rearing and decreased phasic dopamine release while increasing the dopaminergic response to cocaine. In Experiment 2, mice underwent AA-5-HT, ACEA, or vehicle conditioned place preference, then saccharin preference testing, a measure commonly associated with anhedonia. Mice did not develop a conditioned place preference or aversion for AA-5-HT or ACEA, and repeated exposure to AA-5-HT or ACEA did not alter saccharin preference. Altogether, the findings suggest that neither of these drugs induce behaviors that are classically associated with abuse liability in mice; however, direct cannabinoid receptor Type 1 agonism may play more of a role in mediating mesolimbic dopamine functioning than indirect cannabinoid agonism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

CB-0821, a novel CC chemokine receptor 5 (CCR5) inhibitor with improved binding efficacy proposed as anti-HIV candidate: Computational and in vitro approach.

The CC chemokine receptor 5 (CCR5) serves a pivotal role in human immunodeficiency virus 1 (HIV-1) infection by acting as a co-receptor and facilitating the binding of the viral envelope glycoprotein (env). Maraviroc (MVC), a Food and Drug Administration-approved monocarboxylic acid amide, is one of the CCR5 inhibitors employed in HIV treatment. Despite the existence of approved drugs, the emergence of drug resistance underscores the necessity for novel compounds to combat resistance and enhance therapeutic efficacy. In this study, CB-0821, identified from the ChemBridge library, emerged as a promising CCR5 inhibitor. Molecular dynamics simulations indicate comparable dynamic properties for CB-0821 and MVC. In silico comparisons with other CCR5 inhibitors emphasize CB-0821's superior binding affinity, positioning it as a potential lead compound. Evaluations of the dissociation constant (Ki) and absorption, distribution, metabolism, and excretion predictions suggest CB-0821 as a well-tolerated drug. Furthermore, the dose-dependent inhibition of CCR5 by CB-0821 in Peripheral blood mononuclear cells (PBMCs) (ranging from 10 to 200nM) demonstrates efficacy, coupled with nontoxicity to Vero cells at concentrations up to 500nM. These results underscore the potential of CB-0821 in HIV antiviral therapy, calling for additional preclinical validations before advancing to clinical considerations.