The dopamine D2-receptor antagonist prochlorperazine is approved clinically as both an antipsychotic and an antiemetic. Classical antipsychotics like prochlorperazine have been shown to treat the positive symptoms of schizophrenia at occupancies higher than 60% with extrapyramidal symptoms occurring at occupancies over 80%. As an antiemetic, this drug is known to carry a high risk of akathisia and some risk for more severe extrapyramidal symptoms, but the relationship between dosage and D2 receptor occupancies has not been reported. The functional consequences of D2 receptor binding at different occupancy levels also remain unexplored in human subjects. In this study, we performed simultaneous PET and MRI to measure receptor occupancy by competition with [[11]C]raclopride and to assess the concurrent functional hemodynamic response versus prochlorperazine dosage. Additional studies in non-human primates (NHP) were performed for comparison and dose flexibility. In human subjects, the effective dose to achieve 50% occupancy was 1.2 mg/100-kg, indicating that a clinical dose of 10 mg will achieve occupancies greater than 80% in virtually all subjects. In both human subjects and NHP, functional MRI responses showed a rapidly escalating response at occupancies larger than about 60%, a response consistent with autoreceptor-mediated dopamine release. These results provide a functional correlate for the lower edge of the antipsychotic therapeutic occupancy window and confirm that D2 receptor antagonism is ineffective at attenuating post-synaptic function at low occupancies.

Since the publication of the Taiwan Headache Society's 2022 Guidelines for the Acute Treatment of Migraine Attacks, advances in headache medicine and the approval of new drugs in Taiwan have necessitated an update. To address clinical needs, the Guideline Committee of the Taiwan Headache Society reviewed evidence for pharmacological and non-pharmacological acute treatments using evidence-based principles. Drawing from the latest European, American, and international guidelines, and through expert consensus, this revision updates treatment roles, grades of recommendation, efficacy, and adverse-effect profiles. Currently, a broad range of medications is available in Taiwan for acute migraine management, categorised into "specific" and "non-specific" agents. Specific treatments include oral and intranasal triptans, and gepants, i.e., oral calcitonin gene-related peptide (CGRP) receptor antagonists. Non-specific agents include acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs: diclofenac, ibuprofen, naproxen). Injectable prochlorperazine is also strongly recommended. Ergotamine/caffeine combinations are less effective and are second-line agents, while high-dose aspirin is limited by gastrointestinal risk. Considering the potential risk of dependency, tramadol or tramadol/paracetamol combinations should be reserved until all other agents fail, and should be limited to oral forms. Other opioids, such as morphine, butorphanol, etc., lack evidence and are not recommended. Treatment should follow the principle of stratified care: oral NSAIDs for mild disability, with combination analgesics or parenteral NSAIDs as alternatives, and oral or intranasal triptans for moderate to severe disability, ideally administered early. Antiemetics may be added, and combining triptans with NSAIDs enhances efficacy. Rimegepant can be considered a first-line therapy, particularly for patients who are unresponsive or intolerant to triptans, have cardiovascular contraindications, or are at risk of developing medication overuse. In status migrainosus, parenteral corticosteroids with intravenous fluids are advised. Acetaminophen remains first-line for children and pregnant women. To prevent medication-overuse headache, acute treatments, including NSAIDs, acetaminophen, triptans, ergot derivatives, and combination analgesics, should not exceed two days per week, probably with the exception of rimegepant.

Cerebellar and medullary stroke can cause persistent nausea and vomiting that may be resistant to initial antiemetic monotherapy and interfere with oral intake and recovery. Evidence guiding management remains limited. We report a 48-year-old man with diabetes mellitus and acute-to-subacute infarcts involving the inferomedial right cerebellum and posterior right medulla who presented with 10 days of persistent nausea and vomiting accompanied by focal neurologic symptoms. Diabetic gastroparesis was considered, but abdominal imaging and gastric emptying scintigraphy did not support a contributory gastrointestinal cause. Ondansetron and metoclopramide provided only limited or temporary relief. Symptoms improved after sequential escalation to ondansetron, chlorpromazine, prochlorperazine, and amitriptyline; transdermal scopolamine was included in the discharge regimen. Nausea and vomiting were nearly resolved before discharge and fully resolved by three-month follow-up. Because multiple medications were introduced over a short interval and natural neurologic recovery may have contributed, the effect of any individual agent or combination cannot be determined. This case suggests that receptor-diverse pharmacotherapy may be considered when initial treatment fails while underscoring the need for further study of efficacy, safety, and medication sequencing.

Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease for which effective disease-modifying therapies remain limited. This study aimed to derive internally recurrent ALS-associated transcriptional signatures and generate directionally interpretable drug-repositioning hypotheses using a consensus machine-learning framework. Two publicly available transcriptomic datasets from motor cortex (E-MTAB-2325) and blood (E-TABM-940) were analyzed using four feature-selection methods within 100 repetitions of 4-fold cross-validation. Probes recurrently selected in models achieving an accuracy of at least 0.90 were prioritized and examined using COGENA pathway enrichment and Connectivity Map drug-signature analysis. Fifteen qualifying models were obtained for the motor-cortex dataset and 55 for the blood dataset. No exact prioritized gene or probe identifier was shared between the two top-100 signatures, but pathway-level integration identified complementary evidence involving glial and immune regulation, proteostasis and vesicle trafficking, MAPK-related stress signaling, cytoskeletal and extracellular remodeling, and RNA-related processes. The motor-cortex dataset additionally emphasized astroglial support, glutamate handling, and inclusion-body regulation, whereas the blood dataset highlighted cytokine regulation and directionally heterogeneous immune, mitochondrial, and metabolic signals. Deferoxamine and disulfiram showed the clearest reversal-compatible profiles in motor cortex, whereas yohimbic acid and atovaquone showed reversal-compatible profiles in blood. Ciprofloxacin, prochlorperazine, and a compound group led by androsterone instead showed concordant connectivity. The results provide transparent, hypothesis-generating gene, pathway, and compound priorities, but they do not establish biomarkers, therapeutic efficacy, or clinical suitability and require validation in independent cohorts and experimental ALS models.

Schizophrenia management using conventional oral antipsychotic formulations is constrained by poor bioavailability, extensive first-pass metabolism, and dose-related systemic adverse effects. Intranasal drug delivery using nanocarrier systems has emerged as a promising strategy for direct brain targeting by bypassing the blood-brain barrier (BBB) via olfactory and trigeminal pathways, thereby enhancing therapeutic efficacy while minimizing peripheral exposure.

Nausea and vomiting in pregnancy is a common affliction, especially in the early trimesters. This is typically managed at home with doxylamine-pralidoxime or other home remedies. Many women, however, require additional adjuncts to control their symptoms. In this case we present a G2P0 female at 7 weeks gestation who arrived in the emergency department with persistent vomiting for several days. This patient already had a home medication regimen of multiple antiemetics. Additional treatment with ondansetron, prochlorperazine, and metoclopramide via IV administration as well as fluid administration resulted in minimal improvement in her symptoms in the emergency department. After stepwise escalation of antiemetic therapy and fluid resuscitation failed to provide relief, droperidol administration resulted in the rapid and complete resolution of her symptoms. This allowed for a safe discharge rather than admission for hyperemesis gravidarum. This case highlights the utility of droperidol as a rescue antiemetic in pregnancy when conventional therapies prove to be ineffective. This adds to the evidence supporting consideration of droperidol for refractory cases of nausea and vomiting and hyperemesis gravidarum in pregnancy. The purpose of this case report is to describe the safety and efficacy of droperidol in the treatment in refractory nausea and vomiting in pregnancy.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and ranks as the third leading cause of cancer-related fatalities worldwide. Recently, prochlorperazine (PCZ), a synthetic antipsychotic medication, has gained attention for its potential anticancer properties. However, the specific mechanisms underlying its anticancer effects remain unclear. In this study, we have identified that PCZ effectively inhibits the proliferation of HCC cells and diminishes the number and size of HCC foci in the mouse model. Subsequent studies have revealed that PCZ can directly bind to β-catenin and enhance the phosphorylation level of β-catenin. This, in turn, inhibits the Wnt signaling pathway, thereby exerting its anticancer effects. This novel finding sheds light on the potential molecular mechanisms of PCZ as a therapeutic strategy for HCC. In summary, our study provides fresh insights into the utility of PCZ as a therapeutic option for HCC and elucidates its molecular mechanisms.

BACKGROUND: Migraine burden is over twice as high among females than males. Although sex differences are recognized in migraine, robust sex-specific guidance for management remains limited. OBJECTIVE: To systematically review and synthesize current evidence on sex-related clinical differences in migraine, including treatment outcomes and reproductive management, and to provide evidence-based or expert consensus recommendations where high-quality data are lacking. METHODS: A systematic literature review using the PICO framework addressed 24 sex-specific questions across three domains: (1) biological sex differences across the lifespan, (2) sex-specific variations in treatment outcomes, and (3) fertility and reproduction-related management. To address anticipated evidence gaps, a structured Delphi consensus process complemented the review. The protocol was registered in PROSPERO (CRD420251058438). RESULTS: Thirty-seven studies informed 10 evidence summaries. Acute and preventive anti-CGRP therapies seem to show similar efficacy between sexes. For menstrual-related migraine attacks (MM), triptans and lasmiditan are effective, with frovatriptan being recommended for short-term prevention; long-term prevention include topiramate and anti-CGRP mAbs. In pregnancy triptans, greater occipital nerve (GON) blocks, and onabotulinumtoxinA are safe, with GON blocks showing potential efficacy. During breastfeeding, triptans appear to be safe. Anti-CGRP mAbs are equally effective in pre and postmenopausal women. Expert consensus emphasizes the influence of hormonal transitions on migraine expression across sexes and supports the use of acetaminophen, antiemetics, magnesium, NSAIDs, steroids, beta-blockers, amitriptyline, and calcium channel blockers as generally safe in WOCBP and during pregnancy, although some agents have trimester-specific limitations. Efficacy was noted for acetaminophen, sumatriptan, antiemetics, magnesium, propranolol, amitriptyline, and onabotulinumtoxinA. During breastfeeding, acetaminophen, NSAIDs, domperidone, prochlorperazine, magnesium, caffeine, beta-blockers, tricyclics, onabotulinumtoxinA, and GON blocks were considered safe. CONCLUSIONS: Evidence is limited, but sex (likely mediated by sex hormones) influence the clinical course of migraine, and likely treatment response. Limitations include absence of sex-specific analyses in older trials, underrepresentation of men, and scarce reproductive safety data. Integrating sex-based analyses and broadening trial inclusion and more reproductive safety evidence are essential for personalized, equitable migraine care.