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Heliyon Mar 2024Both peripheral neuropathy and depression can be viewed as neurodegeneration's consequences of diabetes, at least in part coexisting with or resulting from...
Both peripheral neuropathy and depression can be viewed as neurodegeneration's consequences of diabetes, at least in part coexisting with or resulting from sodium-calcium dysbalance. This study aims to assess the therapeutic potential of the orally applied reverse-mode inhibitor of the sodium-calcium exchanger (NCX) KB-R7943 in the streptozotocin (STZ) diabetes model in rats. A pilot pharmacokinetic (PK) study with high-performance liquid chromatography with high-resolution tandem mass spectrometric detection revealed higher drug exposure (AUC), lower volume of distribution (Vd) and clearance (Cl), and faster decline of the plasma concentration (ƛ) in rats with diabetes vs. controls. Brain and heart accumulation and urinary excretion of the unmetabolized KB-R7943 at least 24 h were also demonstrated in all rats. However, heart and hippocampus KB-R7943 penetration (AUC/AUC) was higher in controls vs. diabetic rats. The development of thermal, mechanical, and chemical-induced allodynia was assessed with the Cold plate test (CPT), Randall-Stiletto (R-S) test, and 0.5% formalin test (FT). Amitriptyline 10 mg/kg, KB-R7943 5 mg/kg, or 10 mg/kg p.o once daily was applied from the 28th to the 49th day. The body weight, coat status, CPT, R-S, and FT were evaluated on days (-5), 0, and 42. On day 41, a forced swim test and 24-h spontaneous physical activities were assessed. The chronic treatment effects were calculated as % of the maximum. A dose-depended amelioration of neuropathic and depression-like effects was demonstrated. The oral application of KB-R7943 for potentially treating neurodegenerative consequences of diabetes merits further studies. The brain, heart, and kidneys are essential contributors to the PKs of this drug, and their safety involvement needs to be further characterized.
PubMed: 38524546
DOI: 10.1016/j.heliyon.2024.e27367 -
International Journal of Pharmaceutics May 2024Interest in 3D printing has been growing rapidly especially in pharmaceutical industry due to its multiple advantages such as manufacturing versatility, personalization...
Interest in 3D printing has been growing rapidly especially in pharmaceutical industry due to its multiple advantages such as manufacturing versatility, personalization of medicine, scalability, and cost effectiveness. Inkjet based 3D printing gained special attention after FDA's approval of Spritam® manufactured by Aprecia pharmaceuticals in 2015. The precision and printing efficiency of 3D printing is strongly influenced by the dynamics of ink/binder jetting, which further depends on the ink's fluid properties. In this study, Computational Fluid Dynamics (CFD) has been utilized to study the drop formation process during inkjet-based 3D printing for piezoelectric and thermal printhead geometries using Volume of Fluid (VOF) method. To develop the CFD model commercial software ANSYS-Fluent was used. The developed CFD model was experimentally validated using drop watcher setup to record drop progression and drop velocity. During the study, water, Fujifilm model fluid, and Amitriptyline drug solutions were evaluated as the ink solutions. The drop properties such as drop volume, drop diameter, and drop velocity were examined in detail in response to change ink solution properties such as surface tension, viscosity, and density. A good agreement was observed between the experimental and simulation data for drop properties such as drop volume and drop velocity.
Topics: Printing, Three-Dimensional; Tablets; Hydrodynamics; Ink; Viscosity; Technology, Pharmaceutical; Amitriptyline; Computer Simulation; Surface Tension
PubMed: 38522489
DOI: 10.1016/j.ijpharm.2024.124037 -
Gerodontology Mar 2024To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment's effectiveness in patients diagnosed with burning mouth syndrome...
OBJECTIVES
To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment's effectiveness in patients diagnosed with burning mouth syndrome (BMS).
BACKGROUND
Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making.
MATERIALS AND METHODS
This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05).
RESULTS
Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response.
CONCLUSIONS
AMT may be effective in BMS management for most patients.
PubMed: 38515010
DOI: 10.1111/ger.12750 -
Cureus Feb 2024Migraine is a globally prevalent neurological disorder. Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine; however,...
Migraine is a globally prevalent neurological disorder. Amitriptyline, a tricyclic antidepressant, has shown potential as a prophylactic treatment for migraine; however, its role as a first-line medication has been debated. A modified Delphi method was used to develop consensus statements on migraine and its management. The literature review identified knowledge gaps, and two survey rounds were conducted among a panel of experts. Consensus was reached for 12 out of 23 initial survey questions, whereas no consensus was reached for four questions after the deliberation in the second round. The results showed that migraine is highly prevalent among women aged 15-35 years in India. Amitriptyline is an effective monotherapy for prophylactic migraine management, with a recommended initial dose of 5-10 mg. A gradual titration over six months achieves optimal results. Amitriptyline is also safe for managing catamenial migraine and can be used at lower doses during pregnancy to alleviate symptoms. The outcomes of this study emphasize that amitriptyline should be considered as a primary prophylactic treatment for migraine because of its efficacy and safety. The evidence-based consensus achieved is intended to serve as guidance for healthcare practitioners in India, and it is anticipated that such adoption will lead to improvement in patient outcomes and an enhancement in the quality of life for those affected by migraines.
PubMed: 38500929
DOI: 10.7759/cureus.54270 -
Neuropsychopharmacology Reports Jun 2024Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable...
Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61-year-old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51-year-old woman complained of a burning sensation along with oral dryness and crumb-like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb-like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS.
Topics: Humans; Clonazepam; Middle Aged; Burning Mouth Syndrome; Male; Female; Drug Therapy, Combination; Isoindoles; Thiazoles; GABA Modulators
PubMed: 38500267
DOI: 10.1002/npr2.12425 -
Medicine Mar 2024Lipid emulsion has been shown to effectively relieve refractory cardiovascular collapse resulting from toxic levels of nonlocal anesthetics. The goal of this study was... (Review)
Review
Lipid emulsion has been shown to effectively relieve refractory cardiovascular collapse resulting from toxic levels of nonlocal anesthetics. The goal of this study was to examine the effect of lipid emulsions on neuropsychiatric drug-induced toxicity using relevant case reports of human patients, with a particular focus on the Glasgow Coma Scale (GCS) score and corrected QT interval, to analyze drugs that frequently require lipid emulsion treatment. The following keywords were used to retrieve relevant case reports from PubMed: "antidepressant or antipsychotic drug or amitriptyline or bupropion or citalopram or desipramine or dosulepin or dothiepin or doxepin or escitalopram or fluoxetine or haloperidol or olanzapine or phenothiazine or quetiapine or risperidone or trazodone" and "lipid emulsion or Intralipid." Lipid emulsion treatment reversed the corrected QT interval prolongation and decreases in Glasgow Coma Scale scores caused by toxic doses of neuropsychiatric drugs, especially lipid-soluble drugs such as amitriptyline, trazodone, quetiapine, lamotrigine, and citalopram. The log P (octanol/water partition coefficient) of the group which required more than 3 lipid emulsion treatments was higher than that that of the group which required less than 3 lipid emulsion treatments. The main rationale to administer lipid emulsion as an adjuvant was as follows: hemodynamic depression intractable to supportive treatment (88.3%) > lipophilic drugs (8.3%) > suspected overdose or no spontaneous breathing (1.6%). Adjuvant lipid emulsion treatment contributed to the recovery of 98.30% of patients with neuropsychiatric drug-induced toxicity. However, further analyses using many case reports are needed to clarify the effects of lipid emulsion resuscitation.
Topics: Humans; Quetiapine Fumarate; Amitriptyline; Citalopram; Fat Emulsions, Intravenous; Trazodone; Drug-Related Side Effects and Adverse Reactions; Dothiepin
PubMed: 38489675
DOI: 10.1097/MD.0000000000037612 -
Innere Medizin (Heidelberg, Germany) Apr 2024
Topics: Humans; Amitriptyline; Irritable Bowel Syndrome; Analgesics, Non-Narcotic; Diarrhea
PubMed: 38483555
DOI: 10.1007/s00108-024-01682-7 -
Talanta Jun 2024This article describes the synthesis of sorptive phases for bioanalysis based on the modification of cellulose paper with natural beeswax as sorbent, resulting in a...
This article describes the synthesis of sorptive phases for bioanalysis based on the modification of cellulose paper with natural beeswax as sorbent, resulting in a substrate completely renewable and sustainable. The preparation of the sorptive phases consisted of the dissolution of beeswax in hexane, followed by its drop-casting on cellulose paper and subsequent evaporation of the solvent. The beeswax modification of paper renders it hydrophobic, enabling the extraction of the target analytes, i.e., imipramine, desipramine, amitriptyline and trimipramine, via hydrophobic interactions. The main variables affecting the extraction performance were investigated (e.g., pH, ionic strength, extraction time, eluent composition, agitation speed). The analytical workflow combines a straightforward sampling, simultaneous extraction of 30 samples in 1 h, and the rapid (<2 min) determination of the analytes via direct infusion mass spectrometry. The method provided limits of detection in the range 2.0 and 3.2 μg L, and the precision, expressed as relative standard deviation, was better than 5.4 % and 8.5 % for intra and inter-day analyses, respectively. The accuracy, in terms of relative recovery, ranged from 90 % to 121 % using saliva as model biofluid.
Topics: Antidepressive Agents, Tricyclic; Cellulose; Amitriptyline; Waxes
PubMed: 38479029
DOI: 10.1016/j.talanta.2024.125860 -
Computational Biology and Chemistry Jun 2024Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks...
Elucidation of escitalopram oxalate and related antidepressants as putative inhibitors of PTP4A3/PRL-3 protein in hepatocellular carcinoma: A multi-computational investigation.
Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks entailed in many malignancies has given some prominent insights that can be leveraged to create molecular therapeutics for combating HCC. Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands. The density function theory (DFT) and chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters for the chosen ligands were evaluated to comprehend the pharmacokinetics, drug-likeness properties, and bioreactivity of the ligands. The precise interaction mechanism was explored using computational methods such as molecular docking and molecular dynamics (MD) simulation studies to assess the inhibitory effect and the stability of the interactions against the protein of interest. Escitalopram oxalate exhibited a comparatively significant docking score (-7.4 kcal/mol) compared to the control JMS-053 (-6.8 kcal/mol) against the PRL-3 protein. The 2D interaction plots exhibited an array of hydrophobic and hydrogen bond interactions. The findings of the ADMET forecast confirmed that it adheres to Lipinski's rule of five with no violations, and DFT analysis revealed a HOMO-LUMO energy gap of -0.26778 ev, demonstrating better reactivity than the control molecule. The docked complexes were subjected to MD studies (100 ns) showing stable interactions. Considering all the findings, it can be concluded that Escitalopram oxalate and related therapeutics can act as potential pharmacological candidates for targeting the activity of PTP4A3/PRL-3 in HCC.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Protein Tyrosine Phosphatases; Antidepressive Agents; Molecular Docking Simulation; Escitalopram; Neoplasm Proteins; Molecular Dynamics Simulation; Oxalates; Density Functional Theory; Molecular Structure; Antineoplastic Agents
PubMed: 38471352
DOI: 10.1016/j.compbiolchem.2024.108039 -
Environmental Monitoring and Assessment Mar 2024Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal...
Defining the environmental occurrence and distribution of chemicals of emerging concern (CECs), including pharmaceuticals and personal care products (PPCPs) in coastal aquatic systems, is often difficult and complex. In this study, 70 compounds representing several classes of pharmaceuticals, including antibiotics, anti-inflammatories, insect repellant, antibacterial, antidepressants, chemotherapy drugs, and X-ray contrast media compounds, were found in dreissenid mussel (zebra/quagga; Dreissena spp.) tissue samples. Overall concentration and detection frequencies varied significantly among sampling locations, site land-use categories, and sites sampled proximate and downstream of point source discharge. Verapamil, triclocarban, etoposide, citalopram, diphenhydramine, sertraline, amitriptyline, and DEET (N,N-diethyl-meta-toluamide) comprised the most ubiquitous PPCPs (> 50%) detected in dreissenid mussels. Among those compounds quantified in mussel tissue, sertraline, metformin, methylprednisolone, hydrocortisone, 1,7-dimethylxanthine, theophylline, zidovudine, prednisone, clonidine, 2-hydroxy-ibuprofen, iopamidol, and melphalan were detected at concentrations up to 475 ng/g (wet weight). Antihypertensives, antibiotics, and antidepressants accounted for the majority of the compounds quantified in mussel tissue. The results showed that PPCPs quantified in dreissenid mussels are occurring as complex mixtures, with 4 to 28 compounds detected at one or more sampling locations. The magnitude and composition of PPCPs detected were highest for sites not influenced by either WWTP or CSO discharge (i.e., non-WWTPs), strongly supporting non-point sources as important drivers and pathways for PPCPs detected in this study. As these compounds are detected at inshore and offshore locations, the findings of this study indicate that their persistence and potential risks are largely unknown, thus warranting further assessment and prioritization of these emerging contaminants in the Great Lakes Basin.
Topics: Animals; Sertraline; Lakes; Environmental Monitoring; Bivalvia; Anti-Bacterial Agents; Etoposide; Cosmetics; Antidepressive Agents; Pharmaceutical Preparations
PubMed: 38438687
DOI: 10.1007/s10661-023-12119-3