OBJECTIVE: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression. METHODS: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support. The resulting psychedelic experience (Five-Dimensional Altered States of Consciousness questionnaire [5D-ASC] and Emotional Breakthrough Inventory [EBI]) were measured. These proximal variables and outcome 3 weeks post-administration (change in Montgomery-Åsberg Depression Rating Scale [MADRS]) were explored using correlation analysis. RESULTS: The mean intensity of psychedelic effects was dose-related, but distributions of scores for different doses overlapped considerably. Depression response correlated with select aspects of the psychedelic experience overall and for individual doses. At the 25 mg dose, 5D-ASC dimensions Oceanic Boundlessness (Pearson correlation coefficient r = -0.508) and Visual Restructuralization (r = -0.516), and EBI (r = -0·637) were the variables with the strongest correlation to the Week 3 change from Baseline in MADRS score. LIMITATIONS: The existence of correlation does not establish causation and exploratory findings require further replication, preferably in larger independent samples. CONCLUSIONS: The intensity of psychedelic experience overlaps widely across doses and mitigates the risk of unblinding to dose. Correlations between psychedelic experience and outcome suggest specificity in psilocybin's mechanism of action. Quality and intensity of psychedelic experience may be a measure of pharmacodynamic effect and reveal an effective dose response phenomenon for single oral doses.

• Keywords
• Dose-response, Psilocybin, Psychedelic, Psychedelic experience, Randomized-control trial, Treatment-resistant depression,
• MeSH
• Depressive Disorder, Treatment-Resistant * drug therapy   MeSH
• Depressive Disorder, Major drug therapy   MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Hallucinogens * administration & dosage   pharmacology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Psilocybin * pharmacology   administration & dosage   MeSH
• Psychiatric Status Rating Scales MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Hallucinogens * MeSH
• Psilocybin * MeSH

The presented study focused on developing and optimizing a modern electroanalytical platform for the direct quantitative determination of galantamine. This work used different voltammetric methods to use a screen-printed sensor with a working boron-doped diamond electrode (SP/BDDE). Beneficial analytical performance for detecting galantamine was achieved in a Britton-Robinson buffer with pH 3.0. The oxidation peaks at 0.92 V and 1.20 V were followed for electrochemical quantification of galantamine. High-resolution mass spectrometry was used for the first time to analyze the products of preparative electrolysis, and a mechanism for the electrochemical oxidation of galantamine was proposed, which describes the demethylation of galantamine and the further oxidation of the hydroxyl group to a ketone group in the galantamine molecule. Coupled with the optimized parameters of differential pulse voltammetry and square-wave voltammetry on the SP/BDDE detected galantamine in two linear ranges (the first range was from 1.22 μM to 10 μM; the second range was from 10 μM to 200 μM), providing the limit of detection and limit of quantification on a micromolar level (0.50 μM and 1.48 μM, respectively). Amperometry and chronoamperometry were employed to develop a rapid detection method for galantamine. In this approach, galantamine can be detected at a level of 1.08 μM (amperometry at the second peak). The selectivity of the optimized amperometric methods was found to be excellent in the presence of ten times higher concentrations of certain interferences. The practical applicability of the SP/BDDE for detecting galantamine was demonstrated through the analysis of pharmaceutical products and human urine samples. The proposed procedure fully complies with the latest requirements of green analytical chemistry.

• Keywords
• Alkaloids, Drugs, Electrochemical sensor, Galantamine, Green chemistry, Voltammetry,
• MeSH
• Boron * chemistry   MeSH
• Diamond * chemistry   MeSH
• Electrochemical Techniques * methods   MeSH
• Electrodes * MeSH
• Galantamine * analysis   urine   chemistry   MeSH
• Humans MeSH
• Limit of Detection MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Boron * MeSH
• Diamond * MeSH
• Galantamine * MeSH

The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.

• Keywords
• 5‐HT2A, fluorescent sensors, neurotransmitter release, presynaptic, short‐term plasticity, synaptic vesicles,
• MeSH
• Hallucinogens * pharmacology   MeSH
• Rats MeSH
• Cells, Cultured MeSH
• Glutamic Acid * metabolism   MeSH
• Lysergic Acid Diethylamide pharmacology   MeSH
• Cerebral Cortex * drug effects   metabolism   cytology   MeSH
• Neurons * drug effects   metabolism   MeSH
• Rats, Sprague-Dawley MeSH
• Psilocybin pharmacology   MeSH
• Serotonin Agents pharmacology   MeSH
• Synaptic Vesicles drug effects   metabolism   MeSH
• Tryptamines pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Hallucinogens * MeSH
• Glutamic Acid * MeSH
• Lysergic Acid Diethylamide MeSH
• Psilocybin MeSH
• Serotonin Agents MeSH
• Tryptamines MeSH

This study assessed the potential of dried Cayenne pepper (CP; Capsicum annuum L.) as a natural additive to rice bran oil (RBO), grape seed oil (GSO), and virgin olive oil (OO). Key analyses included peroxide and acid values, oxidative stability (Rancimat method), the composition of fatty acids (FAs) (GC-FID method), antioxidant activity (AA; DPPH method), and antimicrobial properties (disc diffusion method). Capsaicin and the dihydrocapsaicin contents in CP were quantified (HPLC-DAD method) as 1499.37 ± 3.64 and 1449.04 ± 5.14 mg/kg DW, respectively. Oleic acid (C18:1cis n9) dominated in OO (69.70%), OO-CP (69.73%), and RBO-CP (38.97%), while linoleic acid (C18:2cis n6) prevailed in RBO (41.34%), GSO (57.93%), and GSO-CP (58.03%). The addition of CP influenced the FA profile, particularly linoleic acid in OO and RBO, and all FAs in GSO. Peroxide and acid values increased significantly in RBO and GSO upon CP addition, but induction times remained unaffected. The strongest AA (77.00 ± 0.13%) was observed in OO-CP. Cayenne pepper significantly enhanced the antioxidant profiles of all oils compared to the counterparts. However, the antimicrobial activity was weak (≤5.0 mm inhibition zones) against tested microorganisms. These findings support CP as a functional additive for enhancing the nutritional and functional properties of gourmet oils, while highlighting the need for further optimization to improve stability and bioactivity.

• Keywords
• Cayenne pepper red, antimicrobial activity, antioxidant activity, fatty acids, health benefits, technological profile, vegetable oils,
• MeSH
• Anti-Infective Agents pharmacology   chemistry   MeSH
• Antioxidants * pharmacology   chemistry   MeSH
• Capsicum * chemistry   MeSH
• Capsaicin analogs & derivatives   pharmacology   analysis   MeSH
• Fatty Acids analysis   MeSH
• Plant Oils chemistry   pharmacology   MeSH
• Olive Oil chemistry   MeSH
• Rice Bran Oil chemistry   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Infective Agents MeSH
• Antioxidants * MeSH
• dihydrocapsaicin MeSH Browser
• Capsaicin MeSH
• Fatty Acids MeSH
• Plant Oils MeSH
• Olive Oil MeSH
• Rice Bran Oil MeSH

BACKGROUND: Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events. METHODS: In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed. RESULTS: A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P = 0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was -1.28 mg per liter (95% CI, -1.81 to -0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups. CONCLUSIONS: Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization). (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

• MeSH
• C-Reactive Protein * analysis   MeSH
• Stroke prevention & control   MeSH
• Double-Blind Method MeSH
• Myocardial Infarction * prevention & control   mortality   MeSH
• Kaplan-Meier Estimate MeSH
• Colchicine * therapeutic use   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Recurrence MeSH
• Secondary Prevention MeSH
• Aged MeSH
• Spironolactone therapeutic use   adverse effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• C-Reactive Protein * MeSH
• Colchicine * MeSH
• Spironolactone MeSH

BACKGROUND: Atherosclerotic cardiovascular diseases (ACVDs), a condition characterised by lipid accumulation in arterial walls, which is often exacerbated by chronic inflammation disorders, is the major cause of mortality and morbidity worldwide. Colchicine, with its first medicinal use in ancient Egypt, is an inexpensive drug with anti-inflammatory properties. However, its role in primary prevention of ACVDs in the general population remains unknown. OBJECTIVES: To assess the clinical benefits and harms of colchicine as primary prevention of cardiovascular outcomes in the general population. SEARCH METHODS: We searched the Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, Web of Science, and LILACS. We searched ClinicalTrials.gov and WHO ICTRP for ongoing and unpublished studies. We also scanned the reference lists of relevant included studies, reviews, meta-analyses, and health technology reports to identify additional studies. There were no limitations on language, date of publication, or study setting. The search results were updated on 31 May 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) in any setting, recruiting adults without pre-existing cardiovascular disease. We included trials that compared colchicine versus placebo, non-steroidal anti-inflammatory drugs, corticosteroids, immunomodulating drugs, or usual care. Our primary outcomes were all-cause mortality, non-fatal myocardial infarction, stroke, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors independently selected studies, extracted data, and performed risk of bias and GRADE assessments. MAIN RESULTS: We identified 15 RCTs (1721 participants randomised; 1412 participants analysed) with follow-up periods ranging from 4 to 728 weeks. The intervention was oral colchicine compared with placebo, immunomodulating drugs, or usual care or no treatment. Due to biases and imprecision, the evidence was very uncertain for all outcomes. All trials but one had a high risk of bias. Five out of seven meta-analyses included fewer than six trials (71.4%). The objectives of the review were to assess cardiovascular outcomes in the general population, but many of the included trials focused on liver disease. Colchicine compared to placebo Colchicine may reduce all-cause mortality compared to placebo in primary prevention, but the evidence is very uncertain (risk ratio (RR) 0.68, 95% confidence interval (CI) 0.51 to 0.91; 6 studies, 463 participants; very low-certainty evidence; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 6 to 67). Colchicine may result in little to no difference in non-fatal myocardial infarction, but the evidence is very uncertain (RR 0.87, 95% CI 0.41 to 1.82; 1 study, 100 participants; very low-certainty evidence). Colchicine may not reduce the incidence of stroke, but the evidence is very uncertain (RR 2.43, 95% CI 0.67 to 8.86; 1 study, 100 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea (RR 3.99, 95% CI 1.44 to 11.06; 8 studies, 605 participants; very low-certainty evidence; number needed to treat for an additional harmful outcome (NNTH) 10, 95% CI 6 to 17), and may have little to no effect on neurological outcomes such as seizure or mental confusion (RR 0.72, 95% CI 0.31 to 1.66; 2 studies, 155 participants; very low-certainty evidence), but the evidence is very uncertain. The effect of colchicine on cardiovascular mortality is also very uncertain (RR 1.27, 95% CI 0.03 to 62.43; 2 studies, 160 participants; very low-certainty evidence). Colchicine may not reduce post-cardiac procedure atrial fibrillation, but the evidence is very uncertain (RR 0.74, 95% CI 0.25 to 2.19; 1 study, 100 participants). We found no trials reporting on pericardial effusion, peripheral artery disease, heart failure, or unstable angina. Colchicine compared to methotrexate (immunomodulating drug) Colchicine may result in little to no difference in all-cause mortality compared to methotrexate, but the evidence is very uncertain (RR 0.42, 95% CI 0.12 to 1.51; 1 study, 85 participants; very low-certainty evidence). We found no trials reporting other cardiovascular outcomes or adverse events for this comparison. Colchicine compared to usual care or no treatment The evidence is very uncertain about the effect of colchicine compared with usual care on all-cause mortality in primary prevention (RR 1.07, 95% CI 0.90 to 1.27; 2 studies, 729 participants; very low-certainty evidence). Regarding adverse events, colchicine may increase the incidence of diarrhoea compared to usual care, but the evidence is very uncertain (RR 3.32, 95% CI 1.56 to 7.03; 2 studies, 729 participants; very low-certainty evidence; NNTH 18, 95% CI 12 to 42). No trials reported other cardiovascular outcomes for this comparison. AUTHORS' CONCLUSIONS: This Cochrane review evaluated the clinical benefits and harms of using colchicine for the primary prevention of cardiovascular events in the general population. Comparisons were made against placebo, immunomodulating medications, or usual care or no treatment. However, the certainty of the evidence for the predefined outcomes was very low, highlighting the pressing need for high-quality, rigorous studies to ascertain colchicine's clinical impact definitively. We identified numerous biases and inaccuracies in the included studies, limiting their generalisability and precluding a conclusive determination of colchicine's efficacy in preventing cardiovascular events. The existing evidence regarding colchicine's potential cardiovascular benefits or harms for primary prevention is inconclusive owing to the limitations inherent in the current studies. More robust clinical trials are needed to bridge this evidence gap effectively.

• MeSH
• Anti-Inflammatory Agents, Non-Steroidal therapeutic use   adverse effects   MeSH
• Anti-Inflammatory Agents therapeutic use   adverse effects   MeSH
• Stroke prevention & control   mortality   MeSH
• Myocardial Infarction * prevention & control   mortality   epidemiology   MeSH
• Cardiovascular Diseases * prevention & control   mortality   MeSH
• Colchicine * therapeutic use   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Cause of Death MeSH
• Primary Prevention * methods   MeSH
• Randomized Controlled Trials as Topic * MeSH
• Bias MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH
• Names of Substances
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• Anti-Inflammatory Agents MeSH
• Colchicine * MeSH

The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed. The novel dually acting prophylactic drug (K1959) did not bring any additional benefit compared to the commonly used pyridostigmine. By contrast, an increase in the therapeutic efficacy of classic antidotal treatment was observed when the novel NMDA receptor antagonist (K2060) was combined with commonly used antidotes (oxime reactivator in combination with atropine). This novel combination reduced the acute toxicity of tabun, soman, and sarin more than two-fold, four-fold, and five-fold, respectively. These results highlight the possibility of NMDA antagonists such as K2060 as a supportive drug for the classic therapy of organophosphorus poisoning.

• Keywords
• Acetylcholinesterase inhibition, Atropine, In vivo testing, NMDA receptor antagonist, Nerve agent, Organophosphorus intoxication, Oxime reactivator, Prophylaxis,
• MeSH
• Antidotes * pharmacology   MeSH
• Atropine pharmacology   therapeutic use   MeSH
• Cholinesterase Inhibitors * pharmacology   MeSH
• Disease Models, Animal * MeSH
• Mice MeSH
• Nerve Agents * poisoning   toxicity   MeSH
• Organophosphates MeSH
• Organophosphate Poisoning drug therapy   prevention & control   MeSH
• Oximes pharmacology   therapeutic use   MeSH
• Cholinesterase Reactivators pharmacology   therapeutic use   MeSH
• Receptors, N-Methyl-D-Aspartate * antagonists & inhibitors   metabolism   MeSH
• Sarin toxicity   poisoning   MeSH
• Soman * poisoning   toxicity   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antidotes * MeSH
• Atropine MeSH
• Cholinesterase Inhibitors * MeSH
• Nerve Agents * MeSH
• Organophosphates MeSH
• Oximes MeSH
• Cholinesterase Reactivators MeSH
• Receptors, N-Methyl-D-Aspartate * MeSH
• Sarin MeSH
• Soman * MeSH
• tabun MeSH Browser

INTRODUCTION: Approximately one-third of all AML patients have a mutation in the Fms-like tyrosine kinase 3 (FLT3) gene, which is associated with a poor prognosis in these individuals. The 2017 approval of midostaurin, the first FLT3 inhibitor, spurred extensive development of more potent and selective inhibitors with an improved safety profile. AREAS COVERED: This review analyzes patent inventions for the treatment of AML using FLT3 inhibitors, covering developments from the earliest to the most recent, disclosed in 2024. Our search using the global Espacenet database identified numerous compounds with low nanomolar inhibitory concentrations against FLT3-ITD and FLT3-TKD mutants. These compounds have shown promise in preclinical studies. Co-inhibition strategies and combinatorial therapies to overcome resistance and enhance anti-leukemic efficacy are also discussed. EXPERT OPINION: Recent patents highlight advances in the field of FLT3 inhibitors with a focus on overcoming resistance, improving selectivity and potency. Future strategies may include third-generation inhibitors such as type III allosteric inhibitors, irreversible inhibitors, or PROTACs. Personalized medicine approaches utilizing genetic profiling to tailor therapies are emphasized. Exploration of novel combination regimens with emerging therapies like CAR T-cell therapy, immune checkpoint inhibitors, and small molecules targeting critical AML pathways is ongoing to further enhance anti-leukemic efficacy.

• Keywords
• Acute myeloid leukemia, FLT3 mutation, Fms-like tyrosine kinase 3, anticancer drug discovery, patent review,
• MeSH
• Leukemia, Myeloid, Acute * drug therapy   genetics   MeSH
• Antineoplastic Agents * pharmacology   MeSH
• Drug Resistance, Neoplasm * MeSH
• Precision Medicine MeSH
• Protein Kinase Inhibitors * pharmacology   MeSH
• Humans MeSH
• Mutation * MeSH
• Patents as Topic * MeSH
• Prognosis MeSH
• Staurosporine analogs & derivatives   pharmacology   MeSH
• fms-Like Tyrosine Kinase 3 * antagonists & inhibitors   genetics   MeSH
• Drug Development MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Antineoplastic Agents * MeSH
• FLT3 protein, human MeSH Browser
• Protein Kinase Inhibitors * MeSH
• midostaurin MeSH Browser
• Staurosporine MeSH
• fms-Like Tyrosine Kinase 3 * MeSH

OBJECTIVES: Stability of concentrations of urinary stone-related metabolites was analyzed from samples of recurrent urinary stone formers to assess necessity and effectiveness of urine acidification during collection and storage. METHODS: First-morning urine was collected from 20 adult calcium-stone forming patients at Tomas Bata Hospital in the Czech Republic. Urine samples were analyzed for calcium, magnesium, inorganic phosphate, uric acid, sodium, potassium, chloride, citrate, oxalate, and urine particles. The single-voided specimens were collected without acidification, after which they were divided into three groups for storage: samples without acidification ("NON"), acidification before storage ("PRE"), or acidification after storage ("POST"). The analyses were conducted on the day of arrival (day 0, "baseline"), or after storage for 2 or 7 days at room temperature. The maximum permissible difference (MPD) was defined as ±20 % from the baseline. RESULTS: The urine concentrations of all stone-related metabolites remained within the 20 % MPD limits in NON and POST samples after 2 days, except for calcium in NON sample of one patient, and oxalate of three patients and citrate of one patient in POST samples. In PRE samples, stability failed in urine samples for oxalate of three patients, and for uric acid of four patients after 2 days. Failures in stability often correlated with high baseline concentrations of those metabolites in urine. CONCLUSIONS: Detailed procedures are needed to collect urine specimens for analysis of urinary stone-related metabolites, considering both patient safety and stability of those metabolites. We recommend specific preservation steps.

• Keywords
• kidney stone formers, preanalytical, specimen preservation, stability, urine, urolithiasis,
• MeSH
• Urinalysis methods   MeSH
• Adult MeSH
• Hydrogen-Ion Concentration MeSH
• Uric Acid urine   MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Calculi * urine   MeSH
• Specimen Handling methods   MeSH
• Recurrence * MeSH
• Urine Specimen Collection methods   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Uric Acid MeSH

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication. Solasodine (SS), a toxic alkaloid from the Solanaceae family, was chosen as the model compound. Complexation was studied using nuclear magnetic resonance (NMR) spectroscopy, molecular modelling, and isothermal titration calorimetry (ITC). NMR in various D2O/DMSO‑d6 media revealed a particularly stable inclusion-type complex, identifying a slow exchange process between the CD and the aminosteroid along with a less significant fast exchange between DMSO and SGM. Using various NMR techniques, the structure and kinetic/thermodynamic parameters of the inclusion complex were explored. Theoretical calculations showed the secondary amino head of SS near the carboxylate ends of the SGM sidechains, facilitating intermolecular ionic interactions. ITC experiments in an aqueous environment provided Ka stability constants of 7.03 × 106 M-1 and 4.17 × 106 M-1 at 25 °C and 37 °C, respectively, similar to previously reported SGM complexes with aminosteroid neuromuscular blockers. Finally, SGM significantly increased cell survival and reduced SS toxicity in mHippoE-14 mouse hippocampal embryonic cells, supporting the hypothesis that SGM could act as an antidote to SS's toxic effects.

• Keywords
• Antidote, Competitive titration, ITC, NMR spectroscopy, Solasodine, Sugammadex,
• MeSH
• Solanaceous Alkaloids * chemistry   pharmacology   MeSH
• Cell Line MeSH
• Hippocampus drug effects   MeSH
• Models, Molecular MeSH
• Mice MeSH
• Sugammadex * chemistry   pharmacology   MeSH
• Thermodynamics MeSH
• Cell Survival drug effects   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Solanaceous Alkaloids * MeSH
• solasodine MeSH Browser
• Sugammadex * MeSH