Folia Pharmacologica Japonica最新文献_第2页

[Iron dysregulation and ferroptosis in heart failure: the dual faces of deficiency and overload]. [铁质失调和心力衰竭的铁下垂：缺铁和超载的双重面孔]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26036

Masafumi Funamoto

引用次数: 0

[Dynamics of memory retrieval in health and diseases]. [健康和疾病中的记忆恢复动力学]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25091

Yuki Takamura, Hiroshi Nomura

{"title":"[Dynamics of memory retrieval in health and diseases].","authors":"Yuki Takamura, Hiroshi Nomura","doi":"10.1254/fpj.25091","DOIUrl":"10.1254/fpj.25091","url":null,"abstract":"Memory retrieval is not a static readout of fixed traces but a dynamic regulatory process where the accessibility of engrams, neuronal ensembles that are active during learning, fluctuates with internal and external states. Recent studies suggest that such variability may support adaptive, selective access to behaviorally relevant memories. Here, we review how contextual, stress-related, bodily, and brain-state factors regulate retrieval via engram state transitions and network-level control. Retrieval is facilitated when the external context or affective state at test matches that at encoding, which enhances reactivation of engram cells. In contrast, social stress can transiently shift engrams into a silent state that is not responsive to natural cues, thereby impairing retrieval. Bodily state also plays a key role: reduced arousal weakens prefrontal top-down suppression of task-irrelevant representations, whereas metabolic hormones such as ghrelin, leptin, and insulin family factors modulate synaptic plasticity and thus the efficiency of engram reactivation. In addition, ultra-slow brain dynamics and inappropriate activation of the default mode network (DMN) can disrupt switching to task-positive networks and lower effective access to stored memories. We discuss how failures of these dynamic regulatory mechanisms may underlie core symptoms of psychiatric and neurological disorders, including trauma-related flashbacks in post-traumatic stress disorder (PTSD), negative memory bias in depression, and cognitive fluctuations in dementia with Lewy bodies. We argue that these insights provide a useful framework for understanding the pathophysiology of these disorders and for developing future interventions that selectively target engram accessibility.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 2","pages":"84-88"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Chemotherapy-induced peripheral neuropathy and sex hormones]. 【化疗引起的周围神经病变与性激素】。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25102

Tomoyoshi Miyamoto, Maho Tsubota, Fumiko Sekiguchi, Atsufumi Kawabata

{"title":"[Chemotherapy-induced peripheral neuropathy and sex hormones].","authors":"Tomoyoshi Miyamoto, Maho Tsubota, Fumiko Sekiguchi, Atsufumi Kawabata","doi":"10.1254/fpj.25102","DOIUrl":"10.1254/fpj.25102","url":null,"abstract":"Chemotherapy-induced peripheral neuropathy (CIPN) frequently develops following treatment of cancer with cytotoxic chemotherapeutics, such as taxanes, platinum-containing agents and vinca alkaloids, and leads to impairment of patients' QOL and dose limitation or cessation of chemotherapy in the worst-case scenario. We have demonstrated that extracellular release of high mobility group box 1 (HMGB1), a nuclear protein, plays a critical role in the developmental process of CIPN, and that thrombomodulin alfa (TMα) capable of degrading HMGB1 in a thrombin-dependent manner prevents CIPN development. Our retrospective cohort study in female patients with breast cancer or gynecological cancer undergoing paclitaxel-based chemotherapy has shown that postmenopausal estrogen decline is a risk factor for the development or aggravation of CIPN. We have also demonstrated that ovariectomy aggravates CIPN in laboratory animals treated with paclitaxel, which is prevented by estrogen supplementation or treatment with TMα. On the other hand, there is evidence from animal studies for inhibition of CIPN by progesterone and of neuropathic pain by androgen. Together, different sex hormones including estrogen may function to limit the development of CIPN, while age-related decline of sex hormones could be a risk for CIPN development. Our study to clarify the effects of sex hormones on HMGB1 behavior during the developmental process of CIPN is still in progress, but we nonetheless propose that TMα capable of inactivating HMGB1 is useful in preventive intervention for cancer patients with high risk of CIPN, e.g., postmenopausal females.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 2","pages":"109-114"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Non-clinical safety assessments using human cells for pediatric drug development]. [利用人类细胞进行儿科药物开发的非临床安全性评估]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26016

Yuta Sakamoto, Mitsuhiko Yamada, Yasunari Kanda, Hiroyuki Kawagishi

{"title":"[Non-clinical safety assessments using human cells for pediatric drug development].","authors":"Yuta Sakamoto, Mitsuhiko Yamada, Yasunari Kanda, Hiroyuki Kawagishi","doi":"10.1254/fpj.26016","DOIUrl":"10.1254/fpj.26016","url":null,"abstract":"Pediatric drug development is an urgent need to provide appropriate therapies for pediatric patients. Because children are undergoing continuous growth and development of their body and organs, pharmacological responses to the same drugs may differ from those observed in adults. Clinical trials in children are essential to evaluate efficacy and safety in pediatric populations; however, pediatric drug development faces multiple challenges, including the limited number of eligible patients. To improve the safety and efficiency of clinical trials, it is important to confirm the safety and efficacy of developing drugs at non-clinical stages. For improving the predictability of human drug responses and promoting alternatives to animal experiments, new approach and methodologies (NAMs), such as human cell-based models and organoids, have been developed and applied in drug development. NAMs which can recapitulate pediatric-specific characteristics have the potential to contribute to appropriate non-clinical assessments of safety and efficacy in pediatrics. Here, we introduce our recent approaches using human cell models for the development of pediatric heart failure therapeutics and for in vitro assessment of drug-induced liver injury risk in pediatrics. In addition, we discuss internal and global efforts to improve non-clinical assessment strategies for pediatric drug development.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 3","pages":"159-163"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[The preclinical profiles and the clinical efficacy and safety of vornorexant (Vorzzz^® tablets), a new orexin receptor antagonist]. [一种新的食欲素受体拮抗剂vornorexant （Vorzzz®片）的临床前概况、临床疗效和安全性]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25096

Haruka Yokota, Yukihiro Chino, Kayoko Shibayama, Shigeyuki Chaki, Yumiko Imadera

{"title":"[The preclinical profiles and the clinical efficacy and safety of vornorexant (Vorzzz® tablets), a new orexin receptor antagonist].","authors":"Haruka Yokota, Yukihiro Chino, Kayoko Shibayama, Shigeyuki Chaki, Yumiko Imadera","doi":"10.1254/fpj.25096","DOIUrl":"10.1254/fpj.25096","url":null,"abstract":"Traditionally, benzodiazepines and non-benzodiazepines have been primary pharmacological treatments for insomnia. The introduction of orexin receptor antagonists has provided safer alternatives. Orexin is a neuropeptide involved in maintaining wakefulness, and blockade of its receptors OX1 and OX2 is considered to promote sleep with minimal disruption to the natural sleep. Vornorexant (Vorzzz® tablets 2.5 mg, 5 mg, 10 mg) is a dual orexin receptor antagonist developed in Japan and approved in August 2025 for insomnia. Designed with a short elimination half-life, vornorexant aims to minimize next-day residual effects-a common limitation of conventional hypnotics. In rat electroencephalogram studies, vornorexant increased both non-REM and REM sleep. Phase I trials confirmed rapid absorption and elimination in healthy volunteers. In Phase III trials, vornorexant improved sleep onset, sleep maintenance, and daytime functioning in both short- and long-term use. In a Phase II trial, improvements in both sleep onset latency and sleep maintenance were observed through polysomnographic assessment, confirming efficacy of the intervention based on objective measures. Regarding safety, an increase in the incidence of somnolence with increasing dose was observed, but no adverse events of major clinical concern were identified. No events of dependence, withdrawal, rebound insomnia, or suicidal ideation/behavior were observed. Consistent with its short elimination half-life, findings from clinical trials indicated that vornorexant at doses up to 10 mg did not impair next-day functioning including driving performance, suggesting minimal residual effects. These findings support vornorexant as a promising new therapeutic option for insomnia, offering both efficacy and safety.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 3","pages":"192-197"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Mechanism of action and clinical trial results of a new drug for amyotrophic lateral sclerosis (ALS), Mecobalamin (Rozebalamin^®) for intramuscular injection, 25 mg]. [肌萎缩性侧索硬化症（ALS）新药甲钴胺（Rozebalamin®）肌内注射用，25 mg的作用机制及临床试验结果]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25066

Tetsuhiro Niidome, Takayuki Ishida

{"title":"[Mechanism of action and clinical trial results of a new drug for amyotrophic lateral sclerosis (ALS), Mecobalamin (Rozebalamin®) for intramuscular injection, 25 mg].","authors":"Tetsuhiro Niidome, Takayuki Ishida","doi":"10.1254/fpj.25066","DOIUrl":"10.1254/fpj.25066","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a progressive, intractable neurodegenerative disease characterized by generalized muscle atrophy and weakness, dysarthria, dysphagia, and respiratory muscle paralysis. Respiratory dysfunction due to muscle weakness is the primary cause of death; without mechanical ventilation, death typically occurs within 2 to 5 years after onset. Mecobalamin, an active form of vitamin B12, is thought to suppress homocysteine-induced neuronal cell death in ALS by acting as a coenzyme for methionine synthase, which catalyzes the conversion of homocysteine to methionine. Since the 1990s, research on neurodegenerative diseases supported by Japan's Ministry of Health, Labour and Welfare has suggested that high-dose mecobalamin may confer clinical benefits in ALS. This led to the initiation of clinical development. A Phase II/III double-blind, placebo-controlled comparative trial was conducted, but did not meet its primary endpoint. Based on these trial findings, an investigator-initiated Phase III placebo-controlled, double-blind comparative trial was conducted primarily at Tokushima University Hospital, targeting patients who developed ALS within one year before starting the trial. The trial demonstrated the efficacy of high-dose mecobalamin in slowing the decline in the Revised ALS Functional Rating Scale total score, which was the primary endpoint. Safety was also confirmed. Based on these results, mecobalamin received regulatory approval in September 2024 for the indication \"slowing the progression of functional impairment in ALS.\" It is expected to offer a new treatment option for patients with ALS.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 2","pages":"115-122"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Androgen-mediated pain-regulatory mechanisms targeting primary sensory neurons]. [针对初级感觉神经元的雄激素介导的疼痛调节机制]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25101

Norikazu Kiguchi

{"title":"[Androgen-mediated pain-regulatory mechanisms targeting primary sensory neurons].","authors":"Norikazu Kiguchi","doi":"10.1254/fpj.25101","DOIUrl":"10.1254/fpj.25101","url":null,"abstract":"Given the sex differences in pain sensitivity and the prevalence of pain disorders, there is a strong need to elucidate their molecular basis. Because sex differences arise from the interactions between genetic factors and postnatal influences mediated by sex hormones, understanding how sex steroid hormones regulate pain is of particular importance. The mechanical pain threshold is lower in females than in males, whereas no sex differences are observed in thermal, chemical or inflammatory pain, consistent with findings in humans. In gonadectomized male mice, the mechanical threshold is decreased, suggesting a correlation between androgen levels and mechanical pain sensitivity. The androgen receptor (AR) is widely expressed in regions involved in pain transmission, with prominent nuclear localization in the dorsal root ganglia of male mice. In nociceptive primary sensory neuron-specific AR-conditional knockout (AR-cKO) male mice, the mechanical pain threshold is markedly reduced compared with wild-type males, whereas other pain modalities remain unchanged. Moreover, systemic androgen administration to female mice increases nuclear AR localization and elevates the mechanical pain threshold one day after treatment, but these effects are abolished in AR-cKO females. These findings demonstrate that androgen signaling in primary sensory neurons represents a key neural substrate underlying sex differences in mechanical pain sensitivity. Additionally, sex differences observed in neuropathic pain models may also be alleviated by androgen action. Further elucidation of how androgens act on their target neuronal populations is expected to advance our understanding of sex- and individual-specific differences in pain.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 2","pages":"102-108"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26067

Yasunari Kanda, Yasuhiro Tsukimi

引用次数: 0

[Role of practical work in education of physiology: nurturing scientific thinking]. 实践工作在生理学教育中的作用：培养科学思维。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25072

Katsuya Hirano

{"title":"[Role of practical work in education of physiology: nurturing scientific thinking].","authors":"Katsuya Hirano","doi":"10.1254/fpj.25072","DOIUrl":"10.1254/fpj.25072","url":null,"abstract":"Undergraduate education in health science professionals consists of lectures, drills, practical work, skill practice and experiments. Lectures constitute a significant portion of the curriculum, as they are the primary opportunity to introduce new fundamental knowledge and concepts to students. Drills, practical work, skill practice and experiments supplement the fundamental knowledge and concepts learned in lectures. Similar strategies are used in physiology education. Practical work in physiology education can be divided into two categories: one for deepening students' understanding of the fundamental knowledge and concepts covered in lectures, and the other for demonstrating the applicability of the fundamental knowledge to clinical practice. Practical work reinforces and deepens students' understanding of the knowledge gained in lectures, but due to time constraints, the number of topics covered in practical work is far fewer than those covered in lectures. Practical work cannot be an effective educational method if it simply supplements lectures; desirably, it should fulfill its own unique purpose independent of lectures. Health science professionals are expected to acquire fundamental skills in scientific thinking. Scientific thinking can be described as the ability to clearly distinguish between facts and opinions and to form opinions based on the facts through logical reasoning. Practical work provides the best and most unique method for cultivating scientific thinking. Practical work thus not only complements lectures, but also has distinct advantages over lectures. Practical work is an important educational method in not only reinforcing knowledge gained through lectures but also cultivating scientific thinking.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"326-329"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Practical training of pharmacology in School of Pharmaceutical Sciences: the present and the future]. 药学院药理学实训：现状与未来

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26006

Hiroshi Katsuki

{"title":"[Practical training of pharmacology in School of Pharmaceutical Sciences: the present and the future].","authors":"Hiroshi Katsuki","doi":"10.1254/fpj.26006","DOIUrl":"10.1254/fpj.26006","url":null,"abstract":"Pharmacology is one of the fundamental academic disciplines in the educational courses of Schools of Pharmaceutical Sciences, and practical training of pharmacology provides profound educational effects. On the other hand, the contents of practical training are increasingly forced to make several changes, which is motivated by several factors such as limitation in budget, concerns on animal welfare and experience of COVID-19 crisis. In Kumamoto University School of Pharmacy, the content of practical training of pharmacology and anatomy has been changed recently to diminish the usage of experimental animals to minimum necessary. For example, experiments on the effects of drugs on blood pressure in rats have been replaced by practical training with software-based simulations. Experiments on the effects of drugs on contraction responses of small intestines have also incorporated software-based simulations, but in addition, students have a chance to observe contraction of mouse small intestines in Magnus preparations. Several movies of pharmacological experiments using animals and isolated organs are provided to students via e-learning system. The other sets of experiments involve drug treatments and surgical operations in mice, and students are encouraged to handle mice by themselves in these experiments. We should continue efforts for improving the contents of practical training, while considering several factors including educational effects benefited from animal experiments and a purpose of Schools of Pharmaceutical Sciences in developing human resources for basic research of pharmaceutical sciences and life sciences.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"320-325"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0