Occasional doses of meclizine are probably acceptable during breastfeeding. Large doses or more prolonged use may cause effects in the infant or decrease the milk supply, particularly in combination with a sympathomimetic such as pseudoephedrine or before lactation is well established.

The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan benefits of these proposed interventions in other models or under different conditions, none of the tested compounds significantly increased lifespan in male or female mice. Notably, astaxanthin, mitoglitazone, and meclizine-previously associated with lifespan extension in the ITP-showed no benefit when administered at different doses or starting at later ages. In females, astaxanthin, late-start mitoglitazone, and pioglitazone were associated with significantly reduced lifespan when pooling the data from all three sites. However, site-specific analysis revealed unusually long lifespans in control females at The Jackson Laboratory, prompting reanalysis using data from the other two sites and only showed a negative effect for mitoglitazone and pioglitazone. This study underscores the importance of rigorous, multi-site testing and highlights the challenges of translating promising initial findings into consistent lifespan benefits at other doses or with alternate starting ages. These results suggest that timing and dosage are critical variables in aging intervention studies and reinforce the need for cautious interpretation of single-site or single-cohort findings.

Vertebrobasilar dolichoectasia (VBD) is a rare condition characterized by dilated and tortuous basilar and/or vertebral arteries. It can be asymptomatic or present as an ischemic stroke, hemorrhage, brainstem/cranial nerve compression, or hydrocephalus. We present a case of a 51-year old woman with a history of transient ischemic attack who presented with persistent vertigo and left-sided weakness and numbness for multiple days. Physical exam was remarkable for the findings of central vertigo and left-sided impairment in sensation and strength. While computed tomography (CT) and magnetic resonance imaging were unremarkable, CT angiography showed a tortuous and dilated basilar artery to 4.9 mm, likely the underlying cause of her symptoms. She was continued on her home aspirin, clopidogrel, and high-intensity atorvastatin and started on meclizine for symptomatic management of vertigo. Although rare, VBD should remain on the differential diagnosis for a variety of patient presentations, especially given its poor prognosis in symptomatic patients.

A straightforward, precise, and rapid UV spectrophotometric method has been developed for the simultaneous determination of meclizine (MEC) and pyridoxine (PYR) in binary mixtures. The approach involved two calibration curves: the first was constructed to quantify PYR directly at 290 nm, while the second was used to calculate the concentration ratio (CR) of the mixture at 230 nm. This second curve was generated by plotting the absorbance ratio (AR) against the concentration ratio (CR = [MEC]/[PYR]). Using the experimentally determined concentration ratio (CRₑₓₚ) and the known PYR concentration, the MEC content was calculated as [MEC] = CRₑₓₚ × [PYR]. The method was validated in accordance with ICH Q2 guidelines and demonstrated reliable and consistent performance. When applied to a pharmaceutical formulation, the results expressed as a percentage of the labeled claim were 100.34% ± 0.47 for MEC and 100.04% ± 0.182 for PYR. Furthermore, statistical comparison with a previously published chromatographic method confirmed the equivalence of the two approaches. These results suggest that the developed method is suitable for routine quality control analysis of pharmaceutical preparations containing MEC and PYR. The linearity ranges were 4-20 µg/mL for meclizine and 6-30 µg/mL for pyridoxine and close to 1.00 for both analytes. Excellent precision was demonstrated, with percent Relative Standard Deviations (RSD%) well below 2%. The method also exhibited high accuracy, with analyte recoveries from tablets formulation 99.62 ± 0.34 and 98.92 ± 0.62 for MEC and PYR, respectively.

Clostridioides difficile, a leading cause of hospital-acquired diarrhea, exerts its virulence through two co-regulated toxins, TcdA and TcdB. Despite their pivotal roles, the discovery of inhibitors targeting their biosynthesis is underexplored. Here, we present a high-throughput screening (HTS) platform designed to identify toxin synthesis inhibitors (TSIs) that minimally impact bacterial growth. The primary screen utilized a C. difficile reporter strain expressing secreted Nano-luciferase (secNluc) under the tcdA promoter, whereby inhibition of secNluc production indicates toxin biosynthesis inhibition. Screening the Prestwick Chemical Library at 10 and 100 µM identified several compounds that reduced secNluc activity. Through counter-screening, we eliminated compounds that caused spectral interference. Orthogonal dose-response assays assessing the effectiveness of inhibiting toxin production without affecting growth identified meclizine, an antihistamine, as the primary antivirulence candidate. Meclizine was confirmed as a TSI by showing that it reduced TcdA and TcdB protein levels, the cytopathic potential of cultures, and tcdA and tcdB transcription as determined by ELISA, cell-rounding assays, and RT-qPCR, respectively. Meclizine significantly altered central carbon metabolism in C. difficile, upregulating carbohydrate transport systems and the conversion of lactate to pyruvate, while downregulating glycolytic genes. These changes were associated with intracellular accumulation of glucose and pyruvate, metabolites known to negatively impact toxin production. Taken together, our findings underscore the utility of the above HTS platform to identify anti-C. difficile TSIs, which can serve as molecular and cellular probes, as well as chemical starting points for developing novel therapeutics for C. difficile infection.

Rationale: Metabolic remodeling occurs during partial hepatectomy (PHx)-induced liver regeneration. Phospholipid remodeling during this process and its subsequent impact on liver regeneration remain unknown. The remnant liver's ability to defend against injury is also essential for normal liver regeneration, although the underlying mechanisms remain unclear. Methods: Phospholipidomics was performed to describe phospholipid remodeling after 70% PHx. Phosphate cytidylyltransferase 2, ethanolamine (PCYT2) was overexpressed in hepatocytes using adeno-associated virus under the thyroxine-binding globulin promoter. An ex vivo liver perfusion system was used to regulate portal pressure. GalNAc-conjugated PEG-PCL nano-particles (NPs) were developed to deliver the PCYT2 inhibitor, meclizine. Results: We found a significant decrease in a series of phosphatidylethanolamine (PE) levels at 1 day after 70% PHx. PCYT2, an enzyme for PE synthesis, was downregulated by PHx. Higher portal pressure-induced shear stress is an early event after PHx. As a target gene of hepatocyte nuclear factor 4α, PCYT2 levels were decreased by higher portal pressure. Hepatocyte-specific PCYT2 overexpression aggravated liver damage after PHx by increasing reactive oxygen species levels, lipid peroxidation, and mitochondrial fragmentation. We observed higher hepatic PCYT2 levels in middle-aged mice than in young mice. PCYT2 inhibition by meclizine facilitates liver regeneration in middle-aged mice. Meclizine is also a blocker of the histamine H1 receptor, a membrane receptor. Therefore, we used NPs to deliver meclizine into cells to better target PCYT2 and prevent potential side effects. NP-meclizine improved liver regeneration in middle-aged mice, demonstrating higher therapeutic efficacy than carrier-free meclizine. Conclusions: Decreased PCYT2 levels and PE content due to increased portal pressure protect hepatocytes from PHx-induced injury. Inhibiting PCYT2 with NP-meclizine promoted normal liver regeneration in middle-aged mice.

Meclizine has been shown to promote bone growth by inhibiting a key signaling pathway involved in achondroplasia (ACH). Earlier studies demonstrated its safety in children with ACH after short-term use. The purpose of this study is to assess the safety and efficacy of meclizine treatment over 26 weeks in children with ACH. This open-label, single-arm, Phase 2 study was conducted at four sites in Japan. Nine children with ACH, aged 5-10 years old, received daily meclizine (12.5 mg/day for those < 20 kg; 25 mg/day for those ≥ 20 kg). This was co-administered with growth hormone therapy for 26 weeks. Safety was monitored through adverse events (AEs), while treatment efficacy was measured by changes in height velocity (cm/year). Secondary measures included the proportion of children achieving a height velocity of ≥ 6 cm/year and changes in arm span growth. Arm span velocity and the proportion of participants reaching ≥ 6 cm/year were evaluated through ad hoc analyses. No serious AEs were reported. Height velocity increased slightly from 4.35 ± 1.36 cm/year pre-treatment to 4.46 ± 1.54 cm/year post-treatment. One participant achieved a height velocity of ≥ 6 cm/year. Mean height increased from 107.48 ± 9.04 to 109.77 ± 8.69 cm over the study period. By contrast, arm span velocity was higher at 6.93 ± 2.50 cm/year, with six children reaching ≥ 6 cm/year. An additive effect of meclizine and growth hormone on promoting height was not observed; however, meclizine may enhance arm span growth in children with ACH.Trial registration number jRCT2041230001.

Vertigo is the perception of motion in the absence of movement, which may be described as a sensation of swaying, tilting, spinning, or feeling unbalanced. Due to highly variable descriptions of vertigo, it is often consolidated into the umbrella descriptor 'dizziness', a very common but imprecise complaint that accounts for over three million emergency department (ED) visits annually. Dizziness can describe so many variable sensations that the use of this imprecise description becomes a dilemma that often misleads the treating provider. Vertigo can be of the vestibular or peripheral origin or be due to non-vestibular or central causes. Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo, accounting for over half of all cases. According to various estimates, a minimum of 20% of patients presenting to the provider with vertigo have BPPV. However, this figure could be an underestimation as BPPV is frequently misdiagnosed. It is crucial to distinguish BPPV from other causes of vertigo as the differential diagnosis includes a spectrum of disease processes ranging from benign to life-threatening. Because of the misleading and vague term 'dizziness' that patients commonly use, the provider must pin down what every patient means by it. It can be often achieved by asking the patient to describe what they are feeling without the use of the word 'dizziness.' Barany first described BPPV in 1921. At that time, characteristic vertigo and nystagmus associated with postural changes were linked to the otolithic organs. In 1952, Dix and Hallpike, during their provocative testing, further described classic nystagmus and moved on to explain that the location of the pathology was the ear proper.

This study presents a sustainable analytical methodology for the simultaneous quantification of the antiemetic drug meclizine (MCZ) and its potentially teratogenic impurity 4-chlorobenzophenone (BZP) using first derivative synchronous fluorescence spectroscopy (FDSFS). The method employs a Δλ of 40 nm followed by first derivatization, enabling the selective determination of MCZ at 275 nm and BZP at 311 nm. Given the clinical importance of MCZ in managing nausea and vomiting during pregnancy (affecting 70%-80% of expectant mothers) and the documented reproductive toxicity of the BZP impurity (capable of crossing the placenta and disrupting fetal development), this method addresses a critical safety concern in pharmaceutical quality control. BZP has been linked to adverse reproductive outcomes, hormonal disruption, and developmental toxicity in animal and human studies, making its detection alongside the parent drug imperative for maternal-fetal safety. The practicality and sustainability were quantitatively assessed using the Blue Applicability Grade Index (BAGI), achieving a remarkable score of 80/100, confirming its superior applicability in routine pharmaceutical analysis. This eco-friendly, sensitive, and selective analytical approach represents a significant advancement in the impurity profiling of meclizine used during pregnancy, offering a sustainable tool for pharmaceutical quality assurance with direct implications for maternal and fetal health protection.