Pharmacology Research & Perspectives最新文献

{"title":"Network Pharmacology Combined With Clinical Retrospective Analysis to Investigate the Potential Mechanisms and Clinical Significance of Folate in Treating Spinal Cord Injury.","authors":"Xiaolei Chu, Jiajia Liang, Jiaojiao Sun, Wenjie Liu, Lei Zhang, Zheng Xing, Qingwen Li, Qi Li","doi":"10.1002/prp2.70233","DOIUrl":"10.1002/prp2.70233","url":null,"abstract":"<p><p>Folate is an indispensable nutrient involved in key biological processes, including enzymatic reactions, DNA replication, metabolic regulation, and methylation. Studies indicate that folate promotes neuronal regeneration and repair in patients with spinal cord injury (SCI); however, its precise mechanisms remain unclear. We employed network pharmacology to identify potential targets of folate for SCI treatment; we conducted a clinical retrospective study, selecting 50 SCI patients and 50 non-SCI control subjects from Tianjin Hospital between 2022 and 2025 to validate predictions by assessing serum folate levels. Network pharmacology identified 1402 folate-related targets and 548 SCI-related targets. Key targets included TNF-α, CASP3, EGF, IL1β, and AKT1. Molecular docking revealed the highest binding affinity between folate and CASP3/TNF-α (-8.5 kcal/mol). Clinical validation demonstrated statistically significant lower folate levels in SCI patients compared to normal levels in non-SCI controls. A strong inverse correlation was observed between folate levels and injury level (r = -0.58, p < 0.001). Folate exerts neuroprotective effects by synergistically regulating neuronal apoptosis, inflammatory responses, and oxidative stress pathways. Clinical data reveal prevalent folate deficiency in SCI patients, and this nutritional deficit may exacerbate secondary injury cascades. We recommend incorporating folate supplementation into comprehensive SCI management protocols.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70233"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of Pharmacology Concept Inventory for Concept-Based Learning: Leveraging Theory, Expert Insights, and Student Perspectives.","authors":"Adeladlew K Netere, Tony Hughes, Anna-Marie Babey, Clare Guilding, Carolina Restini, Martin Hawes, John P Kelly, Elvan Djouma, Jennifer Koenig, Jacqueline E McLaughlin, Olusola Olafuyi, Lynette B Fernandes, Janet Mifsud, Graeme J Sills, Anneke H van Houwelingen, Steven J Tucker, Willmann Liang, Patrik Aronsson, Farhan Ahmad Khan, Tina Hinton, Mark Hernandez, Lindsay Cormier, Roisin Kelly-Laubscher, Fabiana A Caetano Crowley, Marina Junqueira Santiago, Margaret Cunningham, Jennelle Durnett Richardson, Kelly Karpa, Paul J White","doi":"10.1002/prp2.70237","DOIUrl":"10.1002/prp2.70237","url":null,"abstract":"<p><p>Misconceptions in pharmacology can undermine learning and compromise both clinical and scientific reasoning, yet few validated tools exist to identify them. Consequently, we developed and validated the Pharmacology Concept Inventory (PCI), which can be used to identify misconceptions, assess learning gains, and evaluate teaching effectiveness. This PCI was designed based on the IUPHAR-Education Section (IUPHAR-Ed) Core Concepts of Pharmacology Project, addressing eight core concepts: drug efficacy, drug-target interaction, steady-state concentration, structure-activity relationship, drug tolerance, drug bioavailability, volume of distribution, and drug clearance. A triangulated design strategy integrated theoretical frameworks, expert review, and student perspectives. Experts examined quality, content validity, and cognitive alignment. The pilot PCI was then administered to a student cohort to evaluate its psychometric properties, providing preliminary evidence for further refinement. Item-level content validity indices ranged from 0.67 to 1.00, with a scale-level average of 0.93. Seventy students completed the pilot survey, leading to the exclusion of items with low discrimination and reliability. Items on drug-target interaction were removed due to consistently poor performance. The final PCI included 26 items covering seven concepts, with strong discrimination indices (0.36-0.75) and difficulty indices (0.26-0.71). Internal consistency was high (Cronbach's alpha = 0.91), and concept-level reliability ranged from 0.64 to 0.85. The PCI provides strong evidence for identifying misconceptions and assessing learning outcomes through a pre-post-test approach. Although the PCI currently addresses only a subset of concepts, continued refinements informed by surveys and interviews will enhance its utility and expand its scope for concept-based learning and curriculum evaluation.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70237"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147499596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apigenin Protects H9c2 Cells Against Oxygen-Glucose Deprivation/Reperfusion Injury by Regulating Autophagy via the HIF-1α/miR-20a Axis.","authors":"Xiaoxu Zhao, Huihui Li, Yi Yuan, Qingwen Cao, Bo Yu, Wenshu Xue, Gongping Yu, Yao Wang, Xiulong Niu, Yue Wang","doi":"10.1002/prp2.70224","DOIUrl":"10.1002/prp2.70224","url":null,"abstract":"<p><p>As living standards improve and the population ages, cardiovascular disease poses a significant threat to human health. Apigenin, a flavonoid compound found in many fruits and vegetables native to warm climates, is named after celery because it is found in the highest concentrations in this plant. Apigenin exhibits various physiological and pharmacological activities. However, its protective effects on the cardiovascular system and the underlying mechanisms are unclear. The aim of this study is to investigate the role of apigenin and its mechanism in protecting against myocardial cell damage induced by OGD/R in H9c2 rat myocardial cells. MTT experiments demonstrated that apigenin protects cells from OGD/R-induced damage under OGD/R conditions. Molecular mechanism studies showed that apigenin (API) inhibits HIF-1α protein expression and promotes miR-20a expression under OGD/R conditions. This reduces the expression of autophagy-related proteins, inhibits cellular autophagy, and SOD activity. Thus, API exerts a protective effect on cells under OGD/R conditions. These results suggest that apigenin protects cells from oxidative stress damage by inhibiting HIF-1α expression and promoting miR-20a expression, thereby reducing autophagy levels in H9c2 cells under OGD/R conditions.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70224"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13042881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic, Safety, and Immunogenicity Similarity of High- and Low-Concentration Formulations of Adalimumab Biosimilar ABP 501, Adalimumab-Atto.","authors":"Vincent Chow, Muhan Zhou, Daniel T Mytych, Alexander Colbert, Mieke Jill Miller, Iwona Wala, Ahad Sabet, Waldemar Radziszewski","doi":"10.1002/prp2.70236","DOIUrl":"10.1002/prp2.70236","url":null,"abstract":"<p><p>ABP 501, a monoclonal anti-tumor necrosis factor antibody, was the first adalimumab biosimilar approved in the US and EU as a 50 mg/mL formulation. An ABP 501 100 mg/mL high-concentration formulation is also now approved. This study compares pharmacokinetics (PK), safety, and immunogenicity of the low- (ABP 501-LCF) and high-concentration (ABP 501-HCF) formulations in healthy adults. This was a randomized, single-blind, single-dose, parallel-group study in healthy adults. Participants were randomized to receive 40 mg of ABP 501 as HCF or LCF. Primary PK endpoints were area under the concentration-time curve from time 0 extrapolated to infinity (AUC_inf) and maximum observed concentration (C_max) with a 90% confidence interval (CI) for the ratio of least square (LS) geometric means (GM) with a similarity margin of 0.80-1.25. Secondary endpoints included other PK parameters, safety, and immunogenicity. Baseline demographic and other characteristics were comparable between groups. Following study injection, ratios of LS GM (90% CIs) for AUC_inf and C_max between ABP 501-HCF and ABP 501-LCF were 1.04 (0.9634, 1.1297) and 1.06 (0.9960, 1.138), falling within the similarity margin. Both formulations were well tolerated with comparable adverse events. The occurrence of anti-drug antibodies and neutralizing antibodies was comparable between groups. This study demonstrates PK similarity between ABP 501-HCF and ABP 501-LCF following a single subcutaneous injection in healthy adults. Immunogenicity and safety profiles were also similar. Given the totality of evidence of similarity of ABP 501 with adalimumab reference product (RP), it is anticipated that ABP 501-HCF will perform similarly to the RP. Trial Registration: NCT04270747.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70236"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Inflammatory and Oxidative Pathways in Idiopathic Pulmonary Fibrosis: Synergistic Effects of Quercetin and Pirfenidone in Modulating Nrf2/PPAR-γ and TLR-4/NF-κB Pathways.","authors":"Hanaa Wanas, Amira Karam Khalifa, Hossein M Elbadawy, Amany E Hamoud, Mohannad A Almikhlafi, Emad Ali Albadawi, Hadel Mahroos Alghabban, Wejdan Hussain Owaydhah, Amr M Galal","doi":"10.1002/prp2.70229","DOIUrl":"10.1002/prp2.70229","url":null,"abstract":"<p><p>Pulmonary fibrosis (PF) is a progressive condition characterized by inflammation and excessive fibrous tissue formation. Pirfenidone, an FDA-approved drug, slows PF progression through reducing TGF-β production and antioxidant effects. Quercetin (Quer) has emerged as a promising candidate for PF management, exhibiting anti-inflammatory and antioxidant effects and inhibiting collagen synthesis in various tissues. Our study was designed to explore the therapeutic potential of combining Pirf and Quer in mitigating bleomycin-induced lung fibrosis in vivo. Using a bleomycin (BLM)-induced lung fibrosis model, the study evaluated the anti-fibrotic effects of Pirf and Quer, both individually and together. Oxidative stress biomarkers (MDA, SOD, GSH-Px), inflammatory cytokines (TNF-α, IL-1β), and gene expression of NF-κB, PPAR-γ, PI3K, TLR-4, and MAPK were measured to assess the cellular response. BLM exposure markedly upregulated inflammatory markers and oxidative stress, with reducing antioxidant defense mechanisms. Treatment with Pirf moderately decreased these fibrotic changes. Quer, known for its potent antioxidant properties, exhibited a stronger reduction in these parameters. BLM treatment increased the expression of NF-κB, PI3K, TLR-4, and MAPK while Pirf and Quer were shown to reduce them significantly. However, PPAR-γ mRNA levels were reduced by BLM treatment and increased by both Pirf and Quer. Notably, the concomitant administration of Pirf and Quer always provided an augmented effect. The combined administration of Pirf and Quer significantly alleviated BLM-induced lung fibrosis more effectively than either drug alone, suggesting that this combination therapy could enhance anti-fibrotic treatments and should be further investigated in clinical settings.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70229"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147369251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychedelic Therapies for Comorbid Major Depressive Disorder and Chronic Pain: A Review of Putative Mechanisms of Action.","authors":"Jordana Kazdan, Karim S Ladha, M Ishrat Husain","doi":"10.1002/prp2.70238","DOIUrl":"10.1002/prp2.70238","url":null,"abstract":"<p><p>Major Depressive Disorder (MDD) and chronic pain are independently debilitating conditions that frequently co-occur. This comorbidity poses a significant clinical challenge, resulting in greater symptom severity, higher disability, and worse prognosis than either condition alone. Current therapies often address each disorder in isolation, leaving individuals with comorbid MDD and chronic pain underserved. Serotonergic psychedelics such as psilocybin, N,N-dimethyltryptamine (DMT), and Lysergic Acid Diethylamide (LSD) have reemerged as promising therapeutic targets for a range of neuropsychiatric disorders. When combined with psychological support, psychedelics show rapid and sustained antidepressant potential, and preliminary evidence supports analgesic effects. Despite substantial overlap in the biological and psychological processes underlying MDD and chronic pain, research on psychedelics for this comorbidity remains largely unexplored. This narrative review examines putative mechanisms through which psychedelics target symptoms of both MDD and chronic pain. Mechanisms considered include serotonergic modulation via the 5-HT2A receptor, anti-inflammatory effects, neuroplastic changes, altered brain network dynamics, psychological effects, and the influence of set and setting. While most existing evidence comes from populations with either depression or pain alone, the breadth of proposed mechanisms supports psychedelics as a unified therapeutic approach for comorbid MDD and chronic pain. This review provides a compelling rationale for future clinical trials to evaluate psychedelic-assisted therapies for complex neuropsychiatric and medical conditions.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70238"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excessive Apixaban Concentrations in a Bleeding Patient Treated With Pharmacological Reversal and Extracorporal Removal-A Case Report.","authors":"Richard Felix Kraus, Johanna Rosenberger, Alexander Dejaco, Michael Paal, Christina Hart, Ralph Burkhardt, Martin Georg Kees","doi":"10.1002/prp2.70228","DOIUrl":"10.1002/prp2.70228","url":null,"abstract":"<p><p>In trauma, even therapeutic apixaban levels can significantly exacerbate bleeding. In cases of overdose, the risk of prolonged, life-threatening hemorrhage increases substantially, necessitating targeted interventions, such as pharmacological reversal agents. Rapid identification of elevated anticoagulant levels is crucial to initiate specific countermeasures and limit blood loss, and point-of-care testing may facilitate timely treatment. In our case of an extreme overdose of apixaban (max 5664.24 ng/mL, first report of such high amount) has resulted in serious and life-threatening clinical symptoms due to sustained multiple injuries. It is still a debate which therapies prove the most efficacious, whereby the vast surplus of apixaban and the short half-life of andexanet alfa must be considered. This case, in which high apixaban concentration persisted, might help to shed light on these issues.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70228"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive and Behavioral Effects of Levetiracetam in Juvenile Rats.","authors":"Sheetal D Ullal, Ashima G Thomas, Sahana Devadasa Acharya, Vandana Blossom, Rajeshwari Shastry","doi":"10.1002/prp2.70226","DOIUrl":"10.1002/prp2.70226","url":null,"abstract":"<p><p>Epilepsy is a common neurologic disorder; its incidence in childhood is 2.5 per 1000 children. Levetiracetam (LEV) is an antiepileptic drug with a broad spectrum of action used in localized and generalized epilepsies in both adults and children. Studies have shown adverse behavioral effects, such as somnolence, agitation, and nonpsychotic mood disorders in short-term studies. The paucity of properly designed long-term studies to determine the impact of LEV treatment in children encouraged us to analyze the long-term effect of LEV in juvenile Wistar rats. The objective was to study the impact of LEV on cognition and behavior in juvenile rats. Six Wistar rats each were randomly allocated to: Group 1: Control-Received 0.9% NaCl at a dose of 10 mL/kg body weight; 2: Received LEV 200 mg/kg dose; 3: Received LEV 400 mg/kg dose. All drugs were administered once daily orally for 21 days, starting from the third postnatal week to the sixth postnatal week. Compared with the control group, both the 200 mg/kg and 400 mg/kg LEV-treated groups subjected to behavioral paradigms did not decrease learning and memory. Histopathological examination revealed a significant decrease in neuronal density in the dentate gyrus, hippocampus, and frontal cortex in both the 200 mg/kg and 400 mg/kg LEV-treated groups compared with the control group. Although LEV remains a valuable antiepileptic agent, this study highlights the importance of cautious dosing and vigilant monitoring, especially in the long-term use of LEV, as histopathological findings revealed a dose-dependent decrease in the neuronal count.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70226"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147366153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colchicine has Dose-Dependent Therapeutic Effects in a LPS-Induced Experimental Endotoxemia Model.","authors":"Meliksah Demir, Ayse Yesim Gocmen, Esin Ozcelebi, Zuleyha Doganyigit, Aslı Okan Oflamaz, Alper Bektas Iskit","doi":"10.1002/prp2.70239","DOIUrl":"10.1002/prp2.70239","url":null,"abstract":"<p><p>Colchicine is an ancient medication that has long been used for anti-inflammatory properties. Because of unfavorable and toxic consequences of colchicine, selecting an appropriate dose is critical. The effects of three different doses (0.5, 1 or 5 mg/kg) of colchicine were evaluated. To stimulate systemic inflammation, we created an LPS-induced experimental endotoxemia model with 1 mg/kg LPS intraperitoneal injection. Possible therapeutic effects of colchicine were investigated on cytokines, decreased mesenteric artery blood flow and histopathological damage scores. Treatment with 1 mg/kg colchicine reduced the pro-inflammatory cytokines IL-1β, TNF-α, IL-8, and IL-17 to levels comparable to the control group and attenuated the damage caused by LPS in liver and spleen tissues. At a dose of 0.5 mg/kg, colchicine was not able to decrease cytokine levels to those of the control group. In contrast, administration of 5 mg/kg colchicine ameliorated mesenteric blood flow; however, this higher dose caused an increase in cytokine levels. Among three different colchicine doses, 1 mg/kg intraperitoneal dose significantly improved the inflammatory indices and may be considered a suitable option for anti-inflammatory treatment.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70239"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Major Congenital Malformations Associated With the First-Trimester Exposure to Antipsychotics: A Large Claims Database Study.","authors":"Ryo Obara, Takamasa Sakai, Tomofumi Ishikawa, Kei Morishita, Motohiko Adomi, Azusa Hara, Saya Kikuchi, Natsuko Kobayashi, Noriyuki Iwama, Genki Shinoda, Aoi Noda, Masatsugu Orui, Mami Ishikuro, Hiroaki Tomita, Nariyasu Mano, Shinichi Kuriyama, Taku Obara","doi":"10.1002/prp2.70231","DOIUrl":"10.1002/prp2.70231","url":null,"abstract":"<p><p>This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to antipsychotics, using a large claims database in Japan. This retrospective cohort study was based on data from a large claims database in Japan. We used a large claims database from 2010 to 2019. Dates of pregnancy onset and delivery were estimated using the developed algorithms. Overall MCMs were defined according to the International Classification of Diseases, 10th revision codes. To address confounding by indication, the risk of MCM in relation to first-trimester antipsychotic use was evaluated among pregnant women with psychiatric disorders diagnosed before the end of the first-trimester. We compared the prevalence of MCMs among infants born to pregnant women with or without first-trimester exposure to antipsychotics and estimated the weighted odds ratios (wORs) using propensity-score overlap weights. The prevalence of psychiatric diagnoses before the end of the first-trimester was 6291 women among the 91 390 who delivered between 2010 and 2019. Among the 6291 diagnosed with psychiatric disorders, 317 were exposed to any antipsychotics during the first-trimester of pregnancy. The prevalence of overall MCMs among live births was 411 (6.9%) among women unexposed to any antipsychotics and 24 (7.6%) among those exposed. The first-trimester exposure to any antipsychotics was not significantly associated with overall MCMs when wORs were calculated using propensity-score overlap weights (wOR 1.144, 95% confidence intervals 0.727-1.799). Exposure to any antipsychotics during the first-trimester of pregnancy was not associated with an increased risk of overall MCMs in infants.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"14 2","pages":"e70231"},"PeriodicalIF":2.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}