Transdermal delivery of glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide (SEMA, 4113 Da) could replace weekly subcutaneous injections with patient-administered patches, thereby transforming diabetes and obesity management. Oral SEMA offers a non-injectable alternative but achieves only 0.4-1% bioavailability due to gastric degradation and limited absorption efficiency in the stomach. Dissolving microneedles (DMNs) represent an ideal transdermal platform for GLP-1RAs, however, no DMN design reported to date has achieved subcutaneous-equivalent bioavailability for a 4 kDa peptide cargo. Here, we screened a seven-mold MN library (varying needle shape, needle length and inter-needle spacing) using finite element analysis (FEA) of mechanical and skin-penetration performance. The optimal MN-T-1000-800, with the highest insertion force and most complex trapezoidal-stack needle, achieved 90.58% relative bioavailability of SEMA - the highest reported for DMN-mediated GLP-1RA delivery. To validate the generality of FEA framework, a 10-fold smaller cargo, rizatriptan benzoate (RIZ, 391 Da), was selected as model drug. The results showed that, unlike the macromolecule, the optimal geometry for the small molecule was MN-C-800-800, which exhibited a relative bioavailability of 465.40% compared with the commercial oral formulation. The two optimal geometries differed fundamentally in tip sharpness, base volume, and multi-stage profile, mechanistically rationalized by geometry-cargo matching and mechanics-dissolution coupling. We propose a cargo-aware DMN design framework that couples FEA screening with cargo-specific bioavailability validation, providing both an immediate clinical candidate for the transdermal delivery of large and small molecules and a generalizable strategy for translational DMNs development.

Rizatriptan benzoate (RZB), a first-line therapy for the acute treatment of migraine, requires sensitive and reliable monitoring in pharmaceutical formulations and biological matrices to ensure effective quality control and therapeutic drug monitoring. In this work, a sustainable, novel and cost-effective electrochemical sensor was established for the sensitive determination of RZB by modifying a carbon paste electrode (CPE) with nickel-doped zinc oxide nanoparticles (Ni-ZnO NPs) via a simple precipitation procedure. The prepared nanoparticles were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FT-IR), confirming their crystalline nature. The Ni-ZnO/CPE demonstrated remarkable electrocatalytic efficiency for RZB oxidation in phosphate buffer solution at pH 6.0. Utilizing differential pulse voltammetry, the sensor showed linearity over the concentration interval of 0.04-20 µM. Moreover, the sensor showed excellent repeatability and intermediate precision, with relative standard deviation (RSD) values below 1.5%. The sensor was effectively employed for RZB detection in tablets and human plasma, exhibiting adequate recovery rates of 99.71-101.26% and 100.22-101.26%, respectively. The suggested approach revealed favorable analytical performance compared with previously reported DPV procedures, offering a lower limit of detection of 0.01 µM and enhanced sensitivity. Moreover, this is the first reported electrochemical method for RZB that combines drug determination with a comprehensive environmental assessment. Environmental sustainability was assessed utilizing modern metrics for greenness, blueness, and whiteness, and the findings revealed an excellent eco-profile with strong compliance with the principles of green analytical chemistry.

SETD5-related neurodevelopmental disorder is a rare genetic condition caused by a mutation in the SETD5 gene, which has previously been shown to cause intellectual disability (ID) along with dysmorphic facies, behavioral difficulties, congenital heart defects, and developmental delays. This report describes an eight-year-old patient with known SETD5 and inflammatory conditions who presented for evaluation of severe headaches consistent with migraines. This patient had associated photophobia and nausea, as well as pain around the eye that was severe enough to awaken him and was only relieved with rizatriptan. To our knowledge, migraine headaches have not previously been described in association with SETD5-related neurodevelopmental disorder. We hope that by sharing this patient's presentation and medical history, this report will broaden the clinical spectrum of SETD5 and its implications.

Acute encephalopathy in patients with prolonged isotretinoin exposure should prompt careful assessment of undisclosed or non-prescribed medication use. This case suggests a possible association between high cumulative isotretinoin exposure, frequent daily rizatriptan use, and acute encephalopathy, but does not establish a definitive drug-drug interaction, requiring a cautious assessment of causality.

Hydrazides serve as a versatile and valuable functional motif in medicinal chemistry, offering facile access to a diverse array of biologically active molecules. In this work, we establish a general and efficient photochemical protocol for the C-N coupling of aryl bromides with hydrazides, which proceeds with a Ni(II)-bipyridine catalyst and an organic amine base, without the need for an external photosensitizer or any additives. This reaction exhibits an exceptionally wide substrate scope (94 examples) and high tolerance toward diverse functional groups. Its synthetic utility is demonstrated by the efficient synthesis of the drug molecules Celecoxib, SC-560, and Rizatriptan.

Background/Objectives: Migraine may be associated with structural changes in the brain, including the cerebellum and brainstem. Some of these changes reflect the brain's plasticity in adapting to migraine-related alterations, but others may influence the severity of migraines and resistance to treatment. Some studies report changes in cortical thickness among migraine patients, and focal cortical dysplasia (FCD) has been considered a possible cause of these changes. We argued that FCD could contribute to the development of migraine and the severity of its symptoms. To date, there has been no consistent report of FCD occurring in migraine patients. Case: A 29-year-old woman presented with a history of at least 19 years of high-frequency episodic migraine without aura. She experienced motion sickness during childhood and adolescence. Her condition worsened last year, evolving into chronic migraine, which was partially controlled by medications such as amitriptyline and rizatriptan, leading to high-frequency episodic migraines. An MRI conducted in 2024 showed a small area of signal abnormality in the left occipital lobe, believed to represent cortical dysplasia. A follow-up MRI after three months showed no changes in this area. She is currently diagnosed with high-frequency episodic migraine and demonstrated severe migraine-related disability, with a MIDAS score of 25, and a severe impact on daily functioning, with a HIT-6 score of 65. Conclusions: The case involves a worsening migraine that was somewhat alleviated by a pharmacological intervention. FCD may contribute to brain hyperexcitability in this case and her motion-related problems during childhood and adolescence. FCD could also play a role in the increasing severity of her migraines and her partial resistance to medication.

Migraines represent one of the most prevalent and debilitating neurological disorders. In terms of quality-of-life impairment and the degree of disability incurred, severe migraine attacks align with the World Health Organization (WHO) level 7 disability, comparable to conditions such as tetraparesis, psychosis, and dementia. The severity of migraine attacks is influenced not only by the intensity of the headache but also by the severity of accompanying non-pain symptoms, which include nausea, vomiting, photophobia, phonophobia, dizziness, and cognitive impairment, as well as the frequency of recurrence. The presence of nausea or vomiting during a migraine attack is indicative of migraine-associated gastroparesis, which adversely affects the bioavailability and efficacy of oral medications. Consequently, these factors contribute to the limited effectiveness of standard tablet formulations in aborting migraine attacks. This article explores contemporary approaches to treating migraine attacks and new criteria for assessing therapeutic efficacy. Particular emphasis is placed on the effectiveness of orally disintegrating tablets (ODT) of rizatriptan compared with sumatriptan and zolmitriptan. Optimal management of a migraine attack necessitates an individualized approach that considers the severity of the condition, the spectrum of clinical manifestations, and the selection of an appropriate pharmaceutical formulation. Strong evidence supports the assertion that rizatriptan 10 mg ODT (Kaporiza) is one of the most rapid, effective, and convenient options for the abortive treatment of migraine attacks in the majority of patients.

Migraine is recognized as a major neurological disorder characterized by substantial global prevalence, affecting more than one billion individuals worldwide. In 2025, the FDA approved a novel fixed-dose mixture of rizatriptan (RIZ) and meloxicam (MEL) for managing acute migraine. In response, an affordable and sensitive TLC-densitometric strategy was developed for determining MEL and RIZ concurrently in their pure powders and recently approved formulation. The separation process was achieved on a 60F254 silica gel stationary phase employing a moving phase of methanol, ethyl acetate, and 25% aqueous ammonia (9:1:0.05, by volume). The medications were UV-scanned at 254.0 nm. Key chromatographic parameters influencing strategy performance were systematically investigated and optimized. Our strategy was fully validated, consistent with ICH standards, and demonstrated satisfactory linearity over concentration ranges of 2-12 μg/band for MEL and 1-6 μg/band for RIZ, along with good accuracy, robustness, precision, and selectivity, enabling reliable quantification without intrusion from common excipients. Furthermore, the environmental sustainability and overall analytical performance of our strategy were comprehensively assessed utilizing multiple appraisal tools, confirming its favorable environmental profile, balanced analytical performance, and practical applicability compared with previously documented methods. Compared with previously published LC methods, particularly UPLC, our strategy requires lower solvent consumption and reduced energy demand and generates less analytical waste owing to the simultaneous analysis of multiple samples on a single plate, while also offering greater operational simplicity. The ability to simultaneously estimate all analytes in a single TLC run cheaply renders our strategy efficient and well-suited for regular QC testing.

Cortical spreading depression (SD) is the likely cause of migraine aura and a putative headache trigger. Migraine treatments, including triptans and calcitonin gene related peptide (CGRP) receptor antagonists, are limited by poor bioavailability. This study evaluates whether intranasally administered poly lactic co-glycolic acid (PLGA) based hybrid nanoparticles (HNPs) encapsulating rizatriptan (RZT) could provide sustained drug release, enhance brain delivery, and improve therapeutic efficacy against periorbital allodynia triggered by optogenetic SD in mice. CGRP8-37 was conjugated to the nanoparticle surface (HNP-CGRP8-37) and RZT encapsulated whitin HNPs (HNP-RZT). were intranasally administered alone or in combination and compared with intraperitoneal CGRP8-37 and RZT. Formulations were characterized for particle size, zeta potential, and polydispersity index, and assessed for in vitro drug release, cytotoxicity, and in vivo brain RZT concentrations. In the acute SD model, periorbital allodynia was evaluated 1 h after a single SD. In the repeated SD paradigm, seven SDs were induced every other day, and periorbital thresholds were assessed up to 6 days after the final SD. HNPs exhibited uniform particle size (<200 nm), positive zeta potential, and low polydispersity. RZT release from HNP-RZT was sustained in vitro. Intranasal HNP-RZT demonstrated prolonged brain RZT retention compared with intraperitoneal RZT. In the acute SD model, HNP-RZT did not reach statistical significance (p = 0.065), whereas intraperitoneal RZT significantly increased periorbital thresholds. In contrast, in the repeated SD model, HNP-RZT demonstrated delayed but persistent suppression of allodynia compared with intraperitoneal RZT. These findings support the potential of intranasal nanoparticle-based delivery to prolong central exposure of RZT and enhance therapeutic durability in chronic SD conditions.

BACKGROUND: Sex differences in the clinical characteristics of cluster headache (CH) remain controversial in both Eastern and Western studies, and such differences have not been thoroughly investigated among Chinese patients. METHODS: This large-scale, multicenter cohort study included 1,206 patients from 31 provinces across China diagnosed with CH between May 2021 and December 2024, and was conducted within the framework of the Chinese Cluster Headache Register Individual Study. Demographic and clinical data were systematically collected from each participant using an electronic structured questionnaire, and compared all variables between sexes. RESULTS: In total, 1,206 patients were enrolled, with a female-to-male ratio of 1:3.94. Demographic analysis revealed that female patients had an earlier mean age of onset, higher educational attainment, and fewer unhealthy lifestyle factors compared to male patients. Female patients were also more likely to have comorbidities such as migraine (28.28% vs. 15.90%, P < 0.001) and psychological conditions, including anxiety and depression, and to use oral rizatriptan for acute treatment (27.78% vs. 15.80%, P < 0.001). With respect to cranial autonomic symptoms (CASs), female patients experienced eyelid edema (18.85% vs. 12.47%, P = 0.010) and ptosis (56.97% vs. 49.90%, P = 0.048) more frequently, and reported migraine-associated symptoms more often. Conversely, male patients more commonly presented with conjunctival hyperemia (56.03% vs. 38.52%, P < 0.001), rhinorrhea (47.92% vs. 38.93%, P = 0.012), and facial sweating (38.15% vs. 30.74%, P = 0.032). Female patients had significantly higher frequencies of attacks during the early morning hours (2:00–8:00), whereas male patients experienced significantly more attacks during midday (10:00–14:00) and evening (16:00–20:00). CONCLUSION: This study provides the first comprehensive analysis of multidimensional sex differences in Chinese patients with CH, encompassing social characteristics, clinical phenotypes, psychological burden, and circadian attack distribution. These findings offer valuable evidence for developing precision medicine approaches and sex-specific clinical management strategies for CH.