UNASSIGNED: Chronic spontaneous urticaria (CSU) is characterized by urticaria persisting for more than 6 weeks and leading to significant morbidity. Antihistamines, especially sgAH (second generation antihistamines) are the first line of treatment for CSU.
UNASSIGNED: This consensus aimed to review the existing translational research on the receptor occupancy of antihistamines, including levocetirizine, and establish its role in the treatment of CSU. The consensus was led by the Antihistamine Receptor Occupancy Group (AROG) from India, an expert panel of twelve dermatologists from various regions with a mix of institutional and practitioner backgrounds. This consensus analyzed the existing translational research on the receptor occupancy of levocetirizine to establish its clinical efficacy and safety of levocetirizine in the treatment of CSU using the grading of recommendations assessment, development, and evaluation (GRADE) method as compared to the varied SGAH.
UNASSIGNED: Second-generation antihistamines constitute the first step in the therapeutic ladder for managing CSU. Levocetirizine has high bioavailability, a high affinity for and occupancy of the H1 receptor, a rapid onset of action, limited distribution, and minimal hepatic metabolism. It exhibits significant anti-inflammatory effects at clinically relevant concentrations. The marked receptor occupancy translates to better efficacy as compared to similarly dosed SGAH and the lower cost of the molecule makes it an appropriate drug for chronic use. Receptor occupancy should serve as the basis of intra-class head-to-head trials for CSU.

Lysosomes are pivotal in cellular functions and disease, influencing cancer progression and therapy resistance with Acid Sphingomyelinase (ASM) governing their membrane integrity. Moreover, cation amphiphilic drugs (CADs) are known as ASM inhibitors and have anti-cancer activity, but the structural mechanisms of their interactions with the lysosomal membrane and ASM are poorly explored. Our study, leveraging all-atom explicit solvent molecular dynamics simulations, delves into the interaction of glycosylated ASM with the lysosomal membrane and the effects of CAD representatives, i.e., ebastine, hydroxyebastine and loratadine, on the membrane and ASM. Our results confirm the ASM association to the membrane through the saposin domain, previously only shown with coarse-grained models. Furthermore, we elucidated the role of specific residues and ASM-induced membrane curvature in lipid recruitment and orientation. CADs also interfere with the association of ASM with the membrane at the level of a loop in the catalytic domain engaging in membrane interactions. Our computational approach, applicable to various CADs or membrane compositions, provides insights into ASM and CAD interaction with the membrane, offering a valuable tool for future studies.

Objectives: Perennial allergic rhinitis (PAR) is common in Japan. Second-generation antihistamines (SGAs) are commonly used for its treatment; however, it remains unclear which SGA is the most cost-effective. Additionally, the pharmacoeconomics of Japanese Kampo shoseiryuto (which was traditionally prescribed to treat PAR in Japan) remains poorly understood. In this study, we aimed to investigate the effectiveness of various SGAs and shoseiryuto for the treatment of PAR in Japanese outpatients, from the healthcare payer\'s perspective. Methods: The most cost- and clinically effective SGAs were determined from a list of 6 SGAs (bepotastine, 10 mg; cetirizine, 10 mg; ebastine, 10 mg; epinastine, 20 mg; loratadine, 10 mg; and olopatadine, 5 mg) together with shoseiryuto, using the overall improvement rate through a model-based analysis. The time horizon was 28 days. Costs were determined based on the Medical Fee Index in 2020. Deterministic and probabilistic sensitivity analyses were conducted to address the uncertainty of the base-case results. Results: Overall, bepotastine (10 mg) and ebastine (10 mg) were cost-effective. Shoseiryuto was less cost-effective than ebastine (10 mg) (dominated). Ebastine (10 mg) was the most cost-effective option based on deterministic and probabilistic sensitivity analyses. Conclusions: Ebastine (10 mg) was the most cost-effective treatment strategy for PAR among the agents evaluated in this study. This insight could aid in establishing an appropriate formulary for treating PAR in hospitals and communities.

UNASSIGNED: Lately, mast cells (MCs) are increasingly implicated in the pathophysiology of irritable bowel syndrome (IBS). The aim of this systematic review was to assess the efficacy of mast cell directed therapies in reducing the main symptoms of IBS: abdominal pain and changes in stool frequency or consistency.
UNASSIGNED: Pubmed, Web of Science and Scopus were searched until December 19, 2022. Trials evaluating the efficacy of mast cell directed therapies, compared to placebo or any form of control group, were included. Trial selection was performed in two stages: screening titles and abstracts and reviewing full papers identified as relevant, taking into account the inclusion criteria.
UNASSIGNED: The search strategy identified a total of 1.384 citations. Eleven trials on 943 IBS patients and 197 controls were included: ten randomized controlled trials, two of which cross-over trials, and one cohort study. Of the 11 studies included in the systematic review, only three studies were found to be at low risk of bias. This limited evidence suggests a significant overall improvement in the key symptoms after treatment with disodium cromoglycate, ebastine, ketotifen or palmitoylethanolamide-polydatin compared to control groups.
UNASSIGNED: Mast cell modulating therapies could be of significant value in therapy for IBS patients. Further high-quality research is needed to establish the therapeutic efficacy of mast cell targeted therapies in order to draw robust conclusions and improve the clinical management of irritable bowel syndrome.

OBJECTIVE: Allergic rhinitis and chronic idiopathic urticaria are common conditions triggered by environmental irritants, stress, and certain foods. The FDA has recently announced that the efficacy and safety of Ebastine (EBS) have been thoroughly evaluated and confirmed. This study considered using various tools to assess their greenness. We used AGREEprep, analytical eco-scale (ESA), and analytical method volume intensity (AMVI) to evaluate the greenness of the validated stability-indicating method and a forced degradation study. This allowed for easy determination and quantitation of EBS in wastewater and dosage form.
METHODS: The method was established on Symmetry RP-C18 (150mm×4.6mm,5μm) using mobile phase, which can be prepared by mixing buffer solution of pH 3 with acetonitrile in a ratio of (37.5: 62.5, v/v) in addition to dissolving 0.72 gm of sodium lauryl sulfate in the final solution. The separation process was executed at a flow rate of 1.5mL/min and 5μL injection volume with UV detection at 254nm. Linearity was conducted for EBS in the 5-50μg/mL range. Different validation parameters were investigated, including accuracy, precision, robustness, and specificity.
RESULTS: The limits of both detection and quantification were 0.84μg/mL and 2.57μg/mL for EBS. The recovery percentages of EBS were found to be 101.01% and 101.02% for wastewater and pharmaceutical formulations, respectively.
CONCLUSIONS: According to International Council for Harmonisation (ICH) guidelines, a forced degradation study of EBS was evaluated, including acid, base hydrolysis, and oxidative hydrolysis using hydrogen peroxide and photolytic and thermal degradation. The highest degradation was achieved by acid hydrolysis. The safety and efficacy of EBS were evaluated via a safety comparative profile study.

We sought to investigate the utility of ebastine (EBA), a second-generation antihistamine with potent anti-metastatic properties, in the context of breast cancer stem cell (BCSC)-suppression in triple-negative breast cancer (TNBC). EBA binds to the tyrosine kinase domain of focal adhesion kinase (FAK), blocking phosphorylation at the Y397 and Y576/577 residues. FAK-mediated JAK2/STAT3 and MEK/ERK signaling was attenuated after EBA challenge in vitro and in vivo. EBA treatment induced apoptosis and a sharp decline in the expression of the BCSC markers ALDH1, CD44 and CD49f, suggesting that EBA targets BCSC-like cell populations while reducing tumor bulk. EBA administration significantly impeded BCSC-enriched tumor burden, angiogenesis and distant metastasis while reducing MMP-2/-9 levels in circulating blood in vivo. Our findings suggest that EBA may represent an effective therapeutic for the simultaneous targeting of JAK2/STAT3 and MEK/ERK for the treatment of molecularly heterogeneous TNBC with divergent profiles. Further investigation of EBA as an anti-metastatic agent for the treatment of TNBC is warranted.

Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.

Antihistamines are among the most widely used medications in the world. Ebastine is an antihistaminic which is long-acting, second-generation, and selective H1-receptor inverse agonist. I report a twelve-year-and-six-month-old girl with temporary prolongation of the QTc interval caused by acute ebastine intoxication due to TikTok challenge. Initial electrocardiogram showed sinus arrhythmia (72 beats/min) and prolongation of the QTc interval (QTc 482 milliseconds). Gastric lavage was performed. Intravenous fluid was administered, and activated charcoal (1 g/kg/per dose) was given. Electrocardiogram 9 h after drug ingestion showed sinus rhythm and normal QTc interval (QTc 414milliseconds). During follow-up, no electrocardiogram abnormalities were detected with electrocardiogram monitoring. She was discharged on day 2 without any complications. This case report is the first in the literature to show acute intoxication with ebastine due to challenge video on TikTok, which leads to a temporary prolongation of the QTc interval. Also, with this case report, I assert the fact that it is important to properly supervise the use of social media, such as TikTok and to review the content of TikTok videos.

The structure of ebastinium hydrogen fumarate {systematic name: 1-[4-(4-tert-butyl-phen-yl)-4-oxobut-yl]-4-(di-phenyl-meth-oxy)piperidin-1-ium (E)-3-carb-oxy-1-hy-droxy-prop-2-en-1-olate}, C32H40NO2 +·C4H3O4 -, a 1:1 salt formed in the reaction between ebastine and fumaric acid is presented. All examined crystals were found to be twinned by pseudo-merohedry. The structure is extensively disordered, with over half (20 out of 35) its non-hydrogen atoms modelled as lying over two sets of sites. In the crystal, cation-anion pairs are linked by a strong N-H⋯O hydrogen bond [N⋯O = 2.697 (11) Å]. These units inter-act via weaker C-H⋯O and C-H⋯π contacts to form layers lying parallel to the bc plane. The hydrogen fumarate anions are linked by a very short O-H⋯O hydrogen bond [O⋯O = 2.5402 (17) Å], augmented by weak C-H⋯O contacts into pairs of R 2 2(6) ring motifs to form chains that extend parallel to the b-axis direction. Comparisons to similar crystal structures are presented.

Ebastine, a histamine H1 antagonist, nonsedating, belonging to BCS class II is used in the treatment of allergic rhinitis and chronic idiopathic urticaria. The current study was intended in augmenting the aqueous solubility and dissolution rate of ebastine, by formulating a microemulsion system using oleic acid, Transcutol® HP, and Tween®80 as oily phase, cosurfactant, and surfactant, respectively, by the phase titration method. A custom mixture design with optimality D was used to design the formulation by using the Design Expert® Software (Version 11; Stat-Ease, Inc., Minneapolis, MN, USA). Optimization of formulation was performed using the numerical optimization technique, where optimization is based upon the desirability. The optimized formulation was evaluated for transmittance, viscosity, globule size, polydispersity index, zeta potential, drug content, morphological studies, and in vitro studies. The optimized formulation displayed percent cumulative drug release, ranging from 82.9% to 90.6% obtained after dissolution studies and the percent cumulative drug release after diffusion studies ranged from 83.3% to 100%. The in vitro release data were subjected to kinetic treatment. The zero-order and first-order plots were linear and showed the highest values for R2, which indicated mixed-order release. The Higuchi plot was linear, indicating diffusion as the mechanism of release. From Peppas plot, it was further confirmed that the release for dissolution studies was anomalous and for diffusion studies it was zero order. Thus, the studies concluded that the microemulsion technique is a very good approach for enhancing the solubility and dissolution rate of the BCS class II drug ebastine.