Crystalline Forms of Trazodone Dihydrates.
Ontology highlight
ABSTRACT:
SUBMITTER: Plater MJ
PROVIDER: S-EPMC8433896 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Copper has been used as an antimicrobial agent for over a century and is now being added to commercial fungicides. Nanomaterials have attracted much attention due to the special properties they have over their bulk form. We studied nanostructured copper (Cu-NPs), investigating the potential for improved antifungal properties derived from its special properties and studied any effect that the oxidation of copper (CuO-NPs) may have. We conducted this research against Colletotrichum gloeoesporioides, a devastating pathogen to plants/crops worldwide. Research on the effects of copper on this fungus are limited. Our studies showed that nanoforms of copper had significant antifungal activities, with Cu-NPs offering the most sustainable efficacy and was more effective than its oxidative form (CuO-NPs). Scanning Electron Microscopy (SEM) images of the treated pathogen show that the hyphae had a swollen appearance, lost their filamentous structure, and the mycelia had a powder-like structure, indicating the probable destruction of the hyphal tubular cell wall. X-ray Difractogram (XRD) outputs showed substantial changes in the physical characteristics of the Cu-NPs after interaction with the fungus. This is the first report to demonstrate chemo-physical changes in the metal compounds, opening new insights for further studies on the mechanism of copper's antifungal properties.
| S-EPMC7279545 | biostudies-literature
Project description:Over the history of carbon, it is generally acknowledged that Bernal AB stacking of the sp2 carbon layers is the unique crystalline form of graphite. The universal graphite structure is synthesized at 2,600~3,000?°C and exhibits a micro-polycrystalline feature. In this paper, we provide evidence for a metastable form of graphite with an AA' structure. The non-Bernal AA' allotrope of graphite is synthesized by the thermal- and plasma-treatment of graphene nanopowders at ~1,500?°C. The formation of AA' bilayer graphene nuclei facilitates the preferred texture growth and results in single-crystal AA' graphite in the form of nanoribbons (1D) or microplates (2D) of a few nm in thickness. Kinetically controlled AA' graphite exhibits unique nano- and single-crystalline feature and shows quasi-linear behavior near the K-point of the electronic band structure resulting in anomalous optical and acoustic phonon behavior.
| S-EPMC5175192 | biostudies-literature
Project description:Trazodone (TRZ) is a commonly prescribed antidepressant with significant off-label use for insomnia. A recent drug screening revealed that TRZ interferes with sterol biosynthesis, causing elevated levels of sterol precursor 7-dehydrocholesterol (7-DHC). Recognizing the well-documented, disruptive effect of 7-DHC on brain development, we designed a study to analyze TRZ effects during pregnancy. Utilizing an in vivo model and human biomaterial, our studies were designed to also account for drug interactions with maternal or offspring Dhcr7 genotype. In a maternal exposure model, we found that TRZ treatment increased 7-DHC and decreased desmosterol levels in brain tissue in newborn pups. We also observed interactions between Dhcr7 mutations and maternal TRZ exposure, giving rise to the most elevated toxic oxysterols in brains of Dhcr7+/- pups with maternal TRZ exposure, independently of the maternal Dhcr7 genotype. Therefore, TRZ use during pregnancy might be a risk factor for in utero development of a neurodevelopmental disorder, especially when the unborn child is of DHCR7+/- genotype. The effects of TRZ on 7-DHC was corroborated in human serum samples. We analyzed sterols and TRZ levels in individuals with TRZ prescriptions and found that circulating TRZ levels correlated highly with 7-DHC. The abundance of off-label use and high prescription rates of TRZ might represent a risk for the development of DHCR7 heterozygous fetuses. Thus, TRZ use during pregnancy is potentially a serious public health concern.
| S-EPMC7851398 | biostudies-literature
Project description:New pharmaceutically acceptable salts of trazodone (trazodone hydrogen bromide and trazodone 1-hydroxy-2-naphthonic acid) for the treatment of central nervous system disorders are synthesized and described. Although trazodone salts are poorly crystalline, single-crystal X-ray diffraction data for trazodone 1-hydroxy-2-naphthonic acid were collected and analyzed as well as compared to the previously described crystal structure of commercially available trazodone hydrochloride. The powder samples of all new salts were characterized by Fourier transform infrared spectroscopy, X-ray diffraction and 13C solid-state nuclear magnetic resonance spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of carbon chemical shielding constants. The main goal of our research was to find salts with better physicochemical properties and to make an attempt to associate them with both the anion structure and the most prominent interactions exhibited by the protonated trazodone cation. The dissolution profiles of trazodone from tablets prepared from various salts with lactose monohydrate were investigated. The studies revealed that salts with simple anions show a fast release of the drug while the presence of more complex anion, more strongly interacting with the cation, effects a slow-release profile of the active substance and can be used for the preparation of the tables with a delay or prolonged mode of action.
| S-EPMC7867375 | biostudies-literature
Project description:Pharmaceutical salt solvates (dimethyl sulfoxide, DMSO) of the drug triamterene with the coformers acetic, succinic, adipic, pimelic, azelaic and nicotinic acid and ibuprofen are prepared by liquid-assisted grinding and solvent-evaporative crystallization. The modified ΔpKa rule as proposed by Cruz-Cabeza [(2012 ▸). CrystEngComm, 14, 6362-6365] is in close agreement with the results of this study. All adducts were characterized by X-ray diffraction and thermal analytical techniques, including single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermal gravimetric analysis. Hydrogen-bonded motifs combined to form a variety of extended tapes and sheets. Analysis of the crystal structures showed that all adducts existed as salt solvates and contained the amino-pyridinium-carboxyl-ate heterodimer, except for the solvate containing triamterene, ibuprofen and DMSO, as a result of the presence of a strong and stable hemitriamterenium duplex. A search of the Cambridge Structural Database (CSD 5.36, Version 1.18) to determine the frequency of occurrence of the putative supramolecular synthons found in this study showed good agreement with previous work.
| S-EPMC5929377 | biostudies-literature
Project description:There is a paucity of clinical trials for the treatment of pediatric insomnia. This study was designed to predict the doses of trazodone to guide dosing in a clinical trial for pediatric insomnia using physiologically-based pharmacokinetic (PBPK) modeling. Data on the pharmacokinetics of trazodone in children are currently lacking. The interaction potential between trazodone and atomoxetine was also predicted. Doses predicted in the following age groups, with exposures corresponding to adult dosages of 30, 75, and 150 mg once a day (q.d.), respectively, were: (i) 2- to 6-year-old group, doses of 0.35, 0.8, and 1.6 mg/kg q.d.; (ii) >6- to 12-year-old group, doses of 0.4, 1.0, and 1.9 mg/kg q.d.; (iii) >12- to 17-year-old group, doses of 0.4, 1.1, and 2.1 mg/kg q.d. An interaction between trazodone and atomoxetine was predicted to be unlikely. Clinical trials based on the aforementioned predicted dosing are currently in progress, and pharmacokinetic data obtained will enable further refinement of the PBPK models.
| S-EPMC7020267 | biostudies-literature
Project description:Delta (δ) and epsilon (ε) co-crystalline forms of syndiotactic polystyrene with a carboxylic acid guest were obtained by sorption of liquid hexanoic acid in syndiotactic polystyrene films exhibiting delta and epsilon nanoporous-crystalline forms. The characterization study is facilitated by axially stretched syndiotactic polystyrene films, used both for polarized FTIR spectra and for WAXD fiber patterns. Particularly informative are two carbonyl-stretching FTIR peaks, attributed to monomeric and dimeric hexanoic acid. The dichroism of these carbonyl peaks indicates that both delta and epsilon phases are able to include hexanoic acid as isolated guest molecules, while only the epsilon phase is also able to include dimeric hexanoic acid molecules in its crystalline channels. The inclusion of both isolated and dimeric hexanoic acid species in the epsilon form crystalline channels produces extremely fast hexanoic acid uptakes by syndiotactic polystyrene epsilon form films.
| S-EPMC8512363 | biostudies-literature
Project description:BackgroundRecent findings indicate that certain classes of hypnotics that target GABA(A) receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABA(A) receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1) known as ocular dominance plasticity.Methodology/principal findingsAfter a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD) to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg), zaleplon (10 mg/kg), or eszopiclone (1-10 mg/kg), and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG) activity, only trazodone (which did not alter EEG activity) significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity.Conclusions/significanceTaken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions.
| S-EPMC2699540 | biostudies-literature
Project description:Trazodone is a widely used antidepressant that is also useful in the control of agitation and insomnia in Alzheimer's disease. This drug is now recognized as having a new mechanism of action, an effect on the unfolded protein response (UPR) pathway, restoring protein translation and slowing neurodegenerative progression in mice. This mechanism may have a role in dementia-modifying treatment. To explore the effects of trazodone on human cognition and to search for clinical evidence of its putative benefits in human neurodegenerative diseases, a systematic review was conducted for studies that evaluated the effect of a minimum dose of 25 mg of trazodone daily, for at least 1 week, on cognition in adult humans. The search was run in MEDLINE, Web of Science, and CENTRAL from the Cochrane databases, yielding a total of 16 studies after selection. Overall, seven studies showed no effect of trazodone on cognition, five showed a beneficial effect by improving or reducing cognitive decline, and four evidenced impaired cognitive function. Our analysis highlights the possibility of a dose-independent dual effect of trazodone on human cognition, with acute utilization associated with impaired cognitive function and long-term use with preventing cognitive deterioration. There was no clinical evidence that trazodone could be used as a specific treatment of neurodegenerative diseases. Future studies should explore the role of trazodone in the UPR pathway and the implications in neurodegenerative diseases in humans.
| S-EPMC8182348 | biostudies-literature
Project description:Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as Oleptro™; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the management of patients with MDD. Although trazodone is approved for the treatment of depression, evidence supports the use of low-dose trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as part of a combination strategy. Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance.
| S-EPMC3693429 | biostudies-other