This retrospective, controlled study evaluated the clinical outcomes of montelukast sodium combined with desloratadine syrup in pediatric patients with allergic rhinitis. Medical records from 360 children aged 6-12 years treated between October 2021 and November 2024 were reviewed. Patients were classified according to documented treatment as desloratadine monotherapy (Group A, n = 180) or desloratadine plus montelukast (Group B, n = 180). During the 4-week treatment period, Total Nasal Symptom Score (TNSS), Total Non-Nasal Symptom Score (TNNSS), time to symptom improvement, serum immunoglobulin E (IgE), interleukin-13 (IL-13), eosinophil counts, and adverse events were assessed. Group B had lower post-treatment TNSS (4.65 ± 2.12 vs 5.32 ± 2.09, p = 0.003) and TNNSS (1.96 ± 1.43 vs 2.48 ± 1.01, p < 0.001), and rhinorrhea improved sooner (10.38 ± 1.87 vs 13.48 ± 1.20 days, p < 0.001). Greater reductions were also observed in inflammatory markers, including IgE and IL-13 (90.36 ± 22.58 vs 102.78 ± 19.25 ng/L, p < 0.001). Adverse-event rates did not differ significantly (0.56% vs 1.67%; Fisher's exact test, p = 0.623), although only four events were recorded. These findings indicate that combination therapy was associated with greater improvements in clinical symptoms and inflammatory markers than desloratadine monotherapy; however, the retrospective, nonrandomized design and limited safety events require cautious interpretation.

Hepatocellular carcinoma (HCC) remains a major global health burden. We have recently demonstrated the synergistic cytotoxicity elicited by the combination of loratadine, raloxifene, and sorafenib in liver cancer cells. In this study, we investigated the potential mechanistic basis of this novel multi-drug regimen by identifying candidate protein targets of the three drugs. Potential protein targets of each drug were identified using the Drug Affinity Responsive Target Stability (DARTS) assay in protein extracts from the HCC cell line HuH7, and molecular docking was performed to predict binding modes and explore the structural feasibility of these drug-target interactions. Bioinformatics analyses were conducted to predict biological functions, molecular interactions, and clinical relevance. We identified 147 potential candidate DARTS-stabilized proteins for loratadine, 191 for sorafenib, and 157 for raloxifene; a proportion of these candidate proteins maintained a statistically significant association with overall survival in HCC patients: 20.14% for loratadine, 22.93% for raloxifene, and 24.47% for sorafenib. Cross-referencing with public databases confirmed several previously documented targets-complementing our experimental approach-while revealing numerous previously unreported target candidates. Docking analyses predicted favorable binding interactions between the drugs and several proteins, such as the putative complex between loratadine and N-glycanase 1 (NGLY1), whose expression correlates with reduced overall survival in HCC patients. Functional enrichment analysis showed that several targets are involved in hallmarks of cancer. Clinically relevant candidate targets of loratadine, raloxifene, and sorafenib were identified. However, as these candidate protein targets were identified exclusively in HuH7 cells, they may not fully generalize across all HCC models without further validation. Nevertheless, our results suggest that loratadine, raloxifene and sorafenib modulate key pathways involved in tumorigenesis. These findings strengthen the use of this combination as a promising therapeutic strategy for HCC and provide new opportunities for the identification of novel targets, prognostic markers, and molecular vulnerabilities suitable for pharmacological intervention in HCC and other malignancies and diseases.

Sensitive and selective green UV-spectrophotometric univariate and multivariate chemometric methods were developed to resolve the overlapped spectra of rupatadine fumarate (RUP), its impurity desloratadine (DES), and methyl paraben (MP). The univariate approach employed was the dual-wavelength (DW) method. Guided by artificial intelligence (AI) in the selection of the optimal wavelength pair, the determination of RUP was performed at 230 and 284.3 nm, and for MP at 236.6 and 253.8 nm. Among the multivariate methods, ANN demonstrated superior predictive accuracy (lowest RMSEP values), followed by PLS-1 and MCR-ALS, highlighting the power of machine learning for complex mixture resolution, particularly in the presence of the preservative MP. A three-factor, five-level experimental design was adopted to construct a calibration set comprising 25 mixtures with varying component ratios, along with 6 independent validation mixtures. The developed methods were successfully applied to pharmaceutical formulation containing the studied drug and were validated in accordance with International Conference of Harmonization (ICH) guidelines. The results obtained were reliable and reproducible, confirming the suitability of these methods for routine analysis and quality control in laboratories. Moreover, the GLANCE tool (Graphical Layout for Analytical Chemistry Evaluation) offered a clear visual summary of the twelve structured method attributes.

Ayahuasca is a psychoactive botanical brew originating from Amazonian ceremonial traditions, containing monoamine oxidase inhibitors (MAOIs) derived from Banisteriopsis caapi and N,N-dimethyltryptamine from Psychotria viridis or Diplopterys cabrerana. Its use has expanded globally for perceived antidepressant and anti-addictive effects. However, the MAOI content of ayahuasca predisposes users to serotonergic toxicity when combined with other serotonergic agents. We present the case of a 46-year-old man who developed severe serotonin syndrome (SS) complicated by acute respiratory failure after ingesting ayahuasca over three days, followed by over-the-counter dextromethorphan (DXM) and diphenhydramine. He required emergent intubation and intensive care unit (ICU) admission. Management with intravenous benzodiazepines, oral cyproheptadine, and supportive care led to rapid clinical improvement, with extubation on ICU day 2 and discharge on hospital day 3. Severe SS attributable to ayahuasca is rarely documented, and to our knowledge this is the first report of ayahuasca combined with over-the-counter DXM and diphenhydramine producing SS severe enough to cause acute respiratory failure. This case highlights the life-threatening potential of combining ayahuasca with commonly available serotonergic medications and underscores the need for clinician awareness of these interactions.

This document is presented as a narrative guide based on the available evidence, adapted to the pediatric population. Since clinical trials in children are nonexistent, much of the information comes from case reports, narrative reviews, and extrapolation from adult studies. Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity within the central nervous system. It is clinically characterized by a triad of neuromuscular hyperactivity, autonomic instability, and altered mental status. Diagnosis is clinical and relies on recent exposure to serotonergic agents and the application of the Hunter Criteria, which show high sensitivity and specificity in adults and are extrapolated to pediatric patients. Causative agents include selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, analgesics such as tramadol and fentanyl, antibiotics like linezolid, antiemetics, recreational drugs, and herbal supplements. Management involves immediate discontinuation of the offending agent and supportive care, including hydration, benzodiazepines to control agitation, and external cooling measures. In moderate to severe cases, cyproheptadine may be used as a serotonin antagonist. Most patients recover within 24 to 72 hours after appropriate treatment. The prognosis is favorable when the syndrome is recognized early; however, delayed diagnosis can result in serious complications such as rhabdomyolysis, renal failure, or coagulopathies. Prevention relies on cautious prescribing, identification of potential drug interactions, and family education regarding safe medication storage. Further research is needed in pediatric populations to validate diagnostic criteria and optimize therapeutic strategies.

Benjakul (BJK) remedy, traditionally used to balance the four elements, has demonstrated clinical efficacy in relieving inflammation and allergic rhinitis (AR) symptoms. This study investigated differential serum peptide expression in AR patients treated with BJK remedy compared to loratadine using MALDI-TOF MS and LC-MS/MS. MALDI-TOF MS revealed four shared mass peptide patterns that were significantly upregulated (p < 0.05) after 3 and 6 weeks of both treatments. Identifying the peptides, 17β-hydroxysteroid dehydrogenase (17β-HSD) and microtubule-actin cross-linking factor 1 (MACF1) were linked to inflammatory suppression and hormonal balance, while zinc finger CCCH-type containing 4 (ZC3H4) and transducin beta-like protein 3 (TBL3) were associated with the relief of pulmonary fibrosis. Conversely, zinc finger homeobox 3 (ZFHX3) and transformation/transcription domain-associated protein (TRRAP) remained elevated after treatment, potentially promoting persistent inflammation via E2F transcription factor 1- (E2F1-) and E2F transcription factor 4- (E2F4-) mediated transcription. Among 1113 peptides identified by LC-MS/MS (selected using a significance threshold of p < 0.05, without a fixed fold-change cutoff), 6-week treatment with BJK remedy significantly downregulated UBQLN1 (4.562-fold; p = 0.016), suppressing toll-like receptor (TLR) activation and B-cell proliferation. It also upregulated Prostaglandin E synthase 2 (PTGES2) and PDZ and LIM domain protein 2 (PDLIM2) (7.841-fold and 8.697-fold, respectively; p = 0.004 and 0.002), while enhancing antioxidant and immunoregulatory responses via ATP-binding cassette subfamily B member 8 (ABCB8) and ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3). By comparison, 3 weeks loratadine treatment significantly downregulated E2F transcription factor 3 (E2F3) and general transcription factor IIIC subunit 6 (GTF3C6) (p = 0.034 and 0.017) and upregulated CTD small phosphatase like 2 (CTDSPL2), suggesting a distinct but complementary anti-inflammatory mechanism. Together, these findings enhance the understanding of AR pathophysiology and may help to elucidate the mechanisms of BJK remedy and loratadine in treatment, supporting the further development of targeted therapies and biomarkers.

Despite cisplatin (CISP) is broadly employed in cancer therapy, its adverse effects, involving hepatotoxicity, restrict its clinical usage. Thus, this study was designed to explore the prospect of repurposing rupatadine (RUPA), a dual antagonist of histamine and platelet-activating factor (PAF), against CISP-evoked hepatotoxicity in rats. Rats were i.p. injected with CISP (6 mg/kg) for the induction of hepatotoxicity on the 8th day of the study in the presence and absence of RUPA in two dosages (3, 6 mg/kg) orally for 14 days. Different biochemical parameters and histopathological assessments, along with the mechanistic characterizations of the possible protective impact of the RUPA were conducted. Administration of CISP evoked hepatic histopathological modifications and raised serum liver enzyme levels and hepatic MDA content, PAF, and histamine levels, along with diminishing the serum albumin level, hepatic SOD activity, and GSH level. Moreover, CISP remarkably augmented the levels of HMGB1, TLR4, p-NF-κB p65, IL-6, TNF-α, IL-18, IL-1β, NLRP3, and cleaved caspase-1 proteins with an evident decline in the level of IL-10. On the contrary, pretreatment with either RUPA.3 or RUPA.6 dramatically ameliorated these alterations triggered by CISP injection. RUPA counteracts hepatotoxicity evoked by CISP in rats via its anti-oxidative as well as anti-inflammatory properties via repression of hepatic HMGB1/TLR4/NF-κB and thus restricts the activation of NLRP3/caspase-1 signaling cascade.

Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through β-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development.

The generation of N-nitrosamine compounds (NOCs) in drugs presents a critical regulatory challenge owing to their potential mutagenicity and exceptionally strict acceptable intake limits required for patient safety. These impurities arise primarily from the reaction between amine-containing active pharmaceutical ingredients and trace amounts of nitrosating agents (reactive NOx), which contribute to N-nitrosation. Reactive NOx species are frequently found in pharmaceutical excipients. Therefore, efficiently reducing reactive NOx is essential for robust management of the risk posed by NOCs. In this study, we employed ultraviolet (UV) irradiation of excipients as a novel preemptive strategy to reduce reactive NOx levels. Desloratadine was used as a secondary amine model to evaluate the generation of N-nitrosamine in physical mixtures with various excipients. The excipients were exposed to different UV wavelengths (248, 313, and 365 nm), and N-nitrosodesloratadine (NDLRT) generation was quantified after storage under stress conditions. We found that 365 nm UV irradiation was the most effective in reducing reactive NOx under all conditions. In a formulation study, 365 nm UV irradiation successfully reduced NDLRT generation in the tablet by 54-68% compared with the control. Overall, the novel strategy described herein should be useful for reducing NOCs without affecting the quality of drugs.