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.