glutaminergic neurotransmission could ameliorate this phenotype, informing future clinical treatment strategies for GRIA3-associated NDDs [39]. Wang X etal. demon­strated that hydroxide (OH−) ions and chloride (Cl−) ions played signicant roles in the degradation of CBZ, with OH− contributing to approximately 50% of the degra­dation process. Eight transformation products (TPs) were identied during CBZ deg­radation, showing a decreasing trend in toxicity. The toxic disinfection byproducts (DBPs) generated during CBZ degradation fell within the permissible limits set by the World Health Organization and China’s drinking water standards. Although nitrogen-containing DBPs (N-DBPs) exhibited the lowest concentration, they were identied as the main contributors to toxicity, warranting further attention in practi­cal applications. Utilizing advanced oxidation technology involving UV-LED and NH2Cl was shown to be an effective method for degrading active pharmaceutical compounds [40]. Matteo Candeloro etal. conducted a study involving 85 patients (37% female, median age 68years) receiving treatment with either CBZ (n=43, 51%) or phenytoin sodium (n=42, 49%), with 62% initially treated with VKAs and 38% receiving treatment with DOACs. The time in therapeutic range (TTR) for VKA patients was 63%, which improved by year 2. Plasma DOAC levels were lower than expected in a signicant portion of the subjects. The thromboembolism rates (95% condence intervals) in patients treated with VKAs and DOACs were 3.6 (3.1–4.2) and 4.4 (3.5–5.6), respectively. The incidences of major bleeding were 1.8 (1.5–2.1) and 1.5 (1.2–1.9), and the rates of all-cause mortality were 3.6 (3.1–4.2) and 1.5 (1.2–1.9), respectively. The incidences were similar between VKAs and DOACs and between CBZ and phenytoin. Conclusion: The incidence of thromboembolism was greater in patients treated with anticoagulants combined with CBZ or phenytoin sodium. Thrombotic and bleeding events were comparable between VKA and DOAC patients. DOAC levels were lower than expected in 47% of the subjects and did not correlate with clinical outcomes [41]. Wentland L et al. systematically explored methods to enhance the detection of CBZ in undiluted human saliva using polymer lamination devices with screen-printed carbon electrodes. Strategies included adding the anionic surfactant sodium dodecyl sulfate to saliva, ltering saliva to remove larger molecular substances, plasma pretreatment of device electrodes, and sample incubation on electrodes. These techniques enable the quantication of therapeutic CBZ concentrations in saliva without requiring prior dilution [42]. Chan H etal. discovered that vitamin D3 and CBZ mitigate TCDB-induced lysosomal dysfunc­tion, inammation, and histological damage. They found that during CDI, TcdB inhibits the CTNNB1/MITF axis, leading to lysosomal acidication inhibition and SQSTM1/NF-κB signaling activation downstream of macrophages [43]. Vitamin D3 and CBZ counteract CDI by restoring MITF expression and lysosomal function in mice. Bonaccorso etal. evaluated the design of CBZ nanocrystals (NCSs) for naso­brain delivery. Using ultrasonic precipitation and quality-by-design principles, they optimized CBZ NCS formulation variables to achieve the desired product quality attributes. The CBZ NCS exhibited thermal stability, appropriate crystallinity, mor­phology, and adhesion. The reactive surface method, which boasts an error rate of only 2.6%, was shown to be a dependable approach for optimizing CBZ nanocrystals (NNMs) with a size not exceeding 300. Additionally, when cultured in articial

cerebrospinal uid at 37°C, CBZ nanocrystals do not exhibit aggregation or degra­dation, further highlighting their stability under physiological conditions. Preliminary biological studies demonstrated the biocompatibility of CBZ NCSs with olfactory nerve cells. The suspension successfully transitioned to a powder form, offering highly concentrated formulations for maximum drug dose delivery in minimal vol­ume [44]. Suwabe S etal. focused on utilizing amorphous solid dispersion (ASD) technology to enhance drug dissolution. They employed CBZ as a model drug and prepared an ASD using the solvent evaporation method (ASD-1). Through the screening of six water- soluble polymer carriers, the ASD-1 formulation based on polyvinyl alcohol (PVA) demonstrated the highest dissolution rate and yield in the nasal cavity (pH6.0) under experimental conditions. Upon dispersing the CBZ sus­pension with the PVA- ASD- 1 formulation, drug delivery was notably enhanced in rat plasma and brain tissue invivo. Furthermore, the PVA-ASD spray-dried powder for­mulation (PVA- ASD- 2) exhibited improved drug dissolution and transfer invivo. Notably, the spray-dried PVA-ASD-2 formulation demonstrated a greater brain/ plasma ratio than the PVA-ASD-1 suspension formulation. These ndings, sup­ported by physical characterization data, underscore the potential of intranasal agents based on ASD for efcient drug delivery to the brain [45].

mechanisms. Additionally, the study raised clinical considerations, such as the possibility that switching from clonazepam to diazepam could worsen parotid gland abnormalities [54]. Eric William Lutz etal. described a case of recurrent clonazepam withdrawal delirium in postoperative neurosurgical patients, detail­ing a middle-aged man who underwent spinal surgery and who experienced ben­zodiazepine withdrawal delirium. Signicant paranoia and hypereuphoria were observed before surgery and on the fourth day postoperatively after the discon­tinuation of benzodiazepine use. Reintroduction of benzodiazepines alleviated the patient’s symptoms, highlighting the importance of considering benzodiazepine withdrawal in the differential diagnosis of acute delirium, even in patients receiv­ing low or moderate doses. Early counseling and preoperative planning for patients with known discontinuation issues, including contacting psychiatric departments for early drug restart, are crucial [55]. Lichenoid drug eruption caused by clonazepam: Clonazepam, commonly administered for anxiety-related disorders and seizures, is generally associated with few adverse skin reactions. However, a single case of lichenoid drug eruption due to clonazepam has been described. An 81-year-old man with Alzheimer’s disease developed a lichenoid rash after taking clonazepam, characterized by a purple scaly patch on his lower limbs from hip to foot. The rash subsided 2months after the discontinuation of clonazepam and the initiation of corticosteroid treatment. This case underscores the importance of recognizing lichenoid drug eruption as a potential adverse reac­tion to clonazepam administration, emphasizing the need for prompt discontinua­tion of the medication [56].

5. Its use may exacerbate tonic–clonic seizures in patients with mixed seizures, so

etal. showed the high efcacy of intrathecal ethosuximide administration in sup­pressing seizures in a genetic model of intractable epilepsy [71].