N-Cyclohexyltryptamine: freebase, bromide and fumarate
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ABSTRACT:
SUBMITTER: Naeem M
PROVIDER: S-EPMC10439405 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
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Project description:The solid-state structures of the naturally occurring psychoactive tryptamine norpsilocin {4-hy-droxy-N-methyl-tryptamine (4-HO-NMT); systematic name: 3-[2-(methyl-amino)-eth-yl]-1H-indol-4-ol}, C11H14N2O, and its fumarate salt (4-hy-droxy-N-methyl-tryptammonium fumarate; systematic name: bis-{[2-(4-hy-droxy-1H-indol-3-yl)eth-yl]methyl-aza-nium} but-2-enedioate), C11H15N2O+·0.5C4H2O4 2-, are reported. The freebase of 4-HO-NMT has a single mol-ecule in the asymmetric unit joined together by N-H⋯O and O-H⋯O hydrogen bonds in a two-dimensional network parallel to the (100) plane. The ethyl-amine arm of the tryptamine is modeled as a two-component disorder with a 0.895 (3) to 0.105 (3) occupancy ratio. The fumarate salt of 4-HO-NMT crystallizes with a tryptammonium cation and one half of a fumarate dianion in the asymmetric unit. The ions are joined together by N-H⋯O and O-H⋯O hydrogen bonds to form a three-dimensional framework, as well as π-π stacking between the six-membered rings of inversion-related indoles (symmetry operation: 2 - x, 1 - y, 2 - z).
| S-EPMC7133046 | biostudies-literature
Project description:The solid-state structures of the synthetic psychedelic 5-meth-oxy-N,N-di-n-propyl-tryptamine (5-MeO-DPT) {systematic name: N-[2-(5-meth-oxy-1H-indol-3-yl)eth-yl]-N-propyl-propan-1-amine}, C17H25N2O, and its fumarate salt, bis-(5-meth-oxy-N,N-di-n-propyl-tryptammonium) fumarate (systematic name: bis-{N-[2-(5-meth-oxy-1H-indol-3-yl)eth-yl]-N-propyl-propan-1-aminium} but-2-ene-dio-ate), 2C17H25N2O+·C4H2O4 2-, are reported. The freebase has a single tryptamine mol-ecule in the asymmetric unit. The mol-ecules are linked together by N-H⋯N hydrogen bonds in zigzag chains along the [010] direction. The fumarate salt has a single tryptammonium cation and half of a fumarate dianion in the asymmetric unit. The tryptammonium and fumarate ions are held together in one-dimensional chains by a series of N-H⋯O hydrogen bonds. These chains are combinations of R 4 4(22) rings, and C 2 2(14) and C 4 4(28) parallel chains along [001].
| S-EPMC8100262 | biostudies-literature
Project description:The single-inhaler extrafine formulation triple combination beclometasone dipropionate (BDP), formoterol fumarate (FF) plus glycopyrronium bromide (GB) is available for asthma management in adults. Its use in adolescents has not yet been evaluated. This study investigated the pharmacokinetic profile of BDP/FF/GB in adults and adolescents, with the aim of ruling out higher plasma exposure in adolescents compared to adults. In this open-label, non-randomized study, patients with asthma aged 12-17 (adolescents) and 18-64 years (adults) self-administered a single dose of BDP/FF/GB 400/24/50 μg via pressurized metered-dose inhaler (pMDI). The primary objective was to rule out higher systemic exposure to beclometasone 17-monopropionate (B17MP; active metabolite of BDP), formoterol, and GB in terms of the area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUC0-t ) in adolescents versus adults. A total of 40 adolescents and 40 adults entered the study (mean age of 14.8 and 43.6 years, respectively). The primary objective (AUC0-t ) was met, with the upper 90% confidence interval of the geometric mean ratio between adolescents and adults <125% for B17MP (point estimate 79.28 [90% CI 71.19; 88.29]), formoterol (88.68 [77.71; 101.20]) and GB (85.49 [72.96; 100.16]). All secondary pharmacokinetic endpoints supported the primary, with pharmacodynamic (safety) and tolerability results similar in the two populations. In conclusion, systemic exposure to extrafine BDP/FF/GB pMDI in adolescents was not higher than that in adults. Furthermore, there were no safety or tolerability signals to warrant a reduction in the dose of BDP/FF/GB for adolescents with asthma.
| S-EPMC9218519 | biostudies-literature
Project description:Background: An extrafine formulation triple therapy combination of beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium bromide (GB) has been developed for the maintenance treatment of asthma and chronic obstructive pulmonary disease. This study used gamma scintigraphy to evaluate the intrapulmonary and extrapulmonary in vivo deposition of BDP/FF/GB, and the intrapulmonary regional distribution of the deposited formulation. Methods: This open-label uncontrolled nonrandomized single-dose study recruited 10 healthy volunteers and 9 patients with asthma. After a krypton-81m (81mKr) ventilation scan was conducted, subjects inhaled study drug (four inhalations of BDP/FF/GB 100/6/12.5 μg radiolabeled using technetium-99 m [99mTc]) through pressurized metered-dose inhaler, and a series of scintigraphic images were taken. The primary objective was to evaluate intrapulmonary drug deposition of BDP/FF/GB, determined as the percentage of nominal (i.e., metered) dose. Secondary endpoints included central/peripheral deposition ratio (C/P), and the standardized central/peripheral ratio (sC/P; 99mTc aerosol C/P/81mKr gas C/P). Results: All participants completed the study, with all scintigraphy procedures performed at one site. In patients with asthma, mean ± standard deviation intrapulmonary deposition was 25.50% ± 6.81%, not significantly different to that in healthy volunteers (22.74% ± 9.19%; p = 0.4715). Approximately half of the lung dose was deposited in the peripheral region of the lung (fraction deposited 0.52 ± 0.07 and 0.49 ± 0.06 in healthy volunteers and patients with asthma, respectively), resulting in C/P ratios of 0.94 ± 0.25 and 1.06 ± 0.25, respectively, with sC/P ratios of 1.80 ± 0.40 and 1.94 ± 0.38. Deposition patterns were similar in the two populations. BDP/FF/GB was well tolerated. Conclusions: This study confirmed that the extrafine particles delivered by BDP/FF/GB penetrate the peripheral areas of the lungs, with a similar proportion of particles deposited in the central and peripheral regions. Importantly, the deposition patterns were similar in healthy volunteers and patients with asthma, suggesting that disease characteristics are unlikely to impact drug deposition. Clinical Trial Registration number: NCT03795350.
| S-EPMC9416540 | biostudies-literature
Project description:Background and purposeCombining inhaled corticosteroids (ICSs), long-acting β2 -adrenoceptor agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) is recommended to treat severe forms of asthma and chronic obstructive pulmonary disease (COPD). Clinical benefits have been demonstrated for ICS/LABA/LAMA combinations. This study characterized the interaction between the ICS beclomethasone dipropionate, the LABA formoterol fumarate and the LAMA glycopyrronium bromide in human airways.Experimental approachHuman passively sensitized airways and bronchi from COPD donors were stimulated with histamine or carbachol. Tissues were incubated overnight with beclomethasone and then treated with formoterol and glycopyrronium, alone or in triple combination. The interaction was assessed by using Bliss Independence and Unified Theory theorems.Key resultsBeclomethasone/formoterol/glycopyrronium combination synergistically relaxed medium bronchi and small airways. Beclomethasone/formoterol/glycopyrronium combination at 100:6:12.5 combination ratio was a balanced drug mixture leading to very strong synergistic effect on relaxation of medium bronchi (Combination Index: from 0.042 to 0.96) and middle to very strong synergy in small airways (Combination Index: from 0.018 to 0.310). The synergy was related with the activation of intracellular glucocorticoid receptors and Gsα subunit G-protein of β2 -adrenoceptors, leading to the modulation of cyclic AMP-dependent PKA pathway.ConclusionTriple beclomethasone/formoterol/glycopyrronium combination induces synergistic bronchorelaxant effect in medium and small human airways, at least in ex vivo experiments. Further research is needed to confirm these findings in clinical studies in patients with asthma or COPD.
| S-EPMC7042115 | biostudies-literature
Project description:Aclidinium bromide/formoterol fumarate (AB/FF) 400/12 µg is a twice-daily long-acting muscarinic receptor antagonist and long-acting β2 agonist (LAMA/LABA) dual-bronchodilator maintenance therapy used to relieve symptoms and reduce future risk of exacerbations in adults with chronic obstructive pulmonary disease (COPD). To date, there have been several clinical studies and post hoc analyses of AB/FF, assessing treatment outcomes in patients with moderate-to-severe COPD. These studies have looked at a range of outcomes, including lung function parameters, patient-reported symptom scores, quality-of-life measures assessing impaired health and perceived well-being, and the frequency, duration, and severity of exacerbations. In light of the major 2017 revision to the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, and the subsequent updates, we present an update on the latest evidence supporting the efficacy and safety of AB/FF. This review discusses the clinical relevance of the improvements in lung function, symptoms, quality of life, and exacerbations in patients with COPD reported in the phase III and IV trials of AB/FF. Given the current concerns over unnecessary inhaled corticosteroid (ICS) use in COPD, we also touch briefly on the use of blood eosinophils as a biomarker for identifying those patients with COPD already using LAMA/LABA therapy for whom the addition of ICS might be of benefit.
| S-EPMC6535700 | biostudies-literature
Project description:The solid-state structure of the synthetic psychedelic 5-methoxy-N,N-diallyltryptamine (5-MeO-DMT) is reported in its freebase form. The title compound {systematic name: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-(prop-2-en-1-yl)prop-2-en-1-amine), C17H22N2O, has a single tryptamine molecule in the asymmetric unit. The molecules are linked by strong N—H⋯N hydrogen bonds into zigzag chains with graph-set notation C(7) along the [010] direction.
| S-EPMC9462216 | biostudies-literature
Project description:BackgroundCombining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.MethodsIn this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*. Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol). Secondary endpoints were change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24. Safety and tolerability were also assessed.ResultsAt study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001). Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC. Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively. All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.ConclusionsTreatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo. Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.Trial registrationClinicaltrials.gov NCT01437397.
| S-EPMC4213545 | biostudies-literature
Project description:Aclidinium-formoterol 400/12 µg is a long-acting muscarinic antagonist (LAMA) and a long-acting ?2-agonist in a fixed-dose combination used in the management of patients with COPD. This study aimed to assess the cost-effectiveness of aclidinium-formoterol 400/12 µg against the long-acting muscarinic antagonist aclidinium bromide 400 µg.A five-health-state Markov transition model with monthly cycles was developed using MS Excel to simulate patients with moderate-to-severe COPD and their initial lung-function improvement following treatment with aclidinium-formoterol 400/12 µg or aclidinium 400 µg. Health states were based on severity levels defined by Global Initiative for Chronic Obstructive Lung Disease 2010 criteria. The analysis was a head-to-head comparison without step-up therapy, from the NHS Scotland perspective, over a 5-year time horizon. Clinical data on initial lung-function improvement were provided by a pooled analysis of the ACLIFORM and AUGMENT trials. Management, event costs, and utilities were health state-specific. Costs and effects were discounted at an annual rate of 3.5%. The outcome of the analysis was expressed as cost (UK£) per quality-adjusted life-year (QALY) gained. The analysis included one way and probabilistic sensitivity analyses to investigate the impact of parameter uncertainty on model outputs.Aclidinium-formoterol 400/12 µg provided marginally higher costs (£41) and more QALYs (0.014), resulting in an incremental cost-effectiveness ratio of £2,976/QALY. Sensitivity analyses indicated that results were robust to key parameter variations, and the main drivers were: mean baseline forced expiratory volume in 1 second (FEV1), risk of exacerbation, FEV1 improvement from aclidinium-formoterol 400/12 µg, and lung-function decline. The probability of aclidinium-formoterol 400/12 µg being cost-effective (using a willingness-to-pay threshold of £20,000/QALY) versus aclidinium 400 µg was 79%.In Scotland, aclidinium-formoterol 400/12 µg can be considered a cost-effective treatment option compared to aclidinium 400 µg alone in patients with moderate-to-severe COPD.
| S-EPMC5026215 | biostudies-other
Project description:Electronic cigarettes are available in a variety of devices with e-liquids also available in many flavors, and nicotine concentrations, albeit less than 20 mg/mL in Europe. Given the dynamics of these products, it is important to evaluate product content, including labeling, nicotine content versus labeled claim, nicotine form, and other aspects that may help policy decisions and align with the Tobacco Product Directive (TPD). Herein, we performed a study on 86 e-liquids from seven European countries (Croatia, Czech Republic, France, Germany, Italy, Poland, and the United Kingdom) with 34 different liquid brands and 57 different flavors. Nicotine content versus labeled claim, labeling, volume, pH, and nicotine form (i.e., freebase nicotine) were evaluated. From all tested products, eight of them from Germany, Poland, and UK (from 3 to 18 mg/mL), met the ±2% criteria. The ±10% criteria was fulfilled by 50 (58.1%) liquids from all countries. Among 71 liquids which contained nicotine, (one e-liquid labeled as 6 mg/mL had no nicotine level quantified), the amount of freebase nicotine differed from 0 to 97.8%, with a mean value 56.5 ± 35.7. None of the tested liquids had nicotine salt listed in the ingredients. Therefore, a low level of freebase nicotine in some liquids was most likely achieved by added flavorings. All tested liquids presented in this study met the basic requirements of the TPD. There were differences in the scope of information about harmfulness, type of warnings on packaging, attaching leaflets, placing graphic symbols, and discrepancies between the declared and quantified nicotine concentrations.
| S-EPMC8875468 | biostudies-literature