Archiv der Pharmazie最新文献_第9页

Anticonvulsant Action of Thiopyrano[2,3-d]thiazole Derivative Les-3384 as a Promising Antiepileptic Agent (In Vivo and In Silico Studies) 硫吡喃[2,3-d]噻唑衍生物Les-3384作为一种有前途的抗癫痫药的抗惊厥作用（体内和计算机研究）

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-07-03 DOI: 10.1002/ardp.70278

Еduard Davydov, Mykhailo Hoidyk, Andrii Lozynskyi, Sergii Shtrygol, Andriy Karkhut, Svyatoslav Polovkovych, Olexandra Roman, Dmytro Khyluk, Hailie Uren, Roman Lesyk

{"title":"Anticonvulsant Action of Thiopyrano[2,3-d]thiazole Derivative Les-3384 as a Promising Antiepileptic Agent (In Vivo and In Silico Studies)","authors":"Еduard Davydov, Mykhailo Hoidyk, Andrii Lozynskyi, Sergii Shtrygol, Andriy Karkhut, Svyatoslav Polovkovych, Olexandra Roman, Dmytro Khyluk, Hailie Uren, Roman Lesyk","doi":"10.1002/ardp.70278","DOIUrl":"10.1002/ardp.70278","url":null,"abstract":"<div>\u0000 \u0000 A novel thiopyrano[2,3-d]thiazole derivative Les-3384 (rel-N-(4-chlorophenyl)-3-[(5aR,11bR)-2-oxo-5a,11b-dihydro-2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d]thiazol-3(6H)-yl]propanamide) was evaluated for its anticonvulsant action. Anticonvulsant activity in mice was assessed using seizure models induced by picrotoxin, thiosemicarbazide, strychnine, caffeine, camphor action, or maximal electroshock (MES). Les-3384 was administered orally at 100 mg/kg. For comparison, valproate, carbamazepine, and inosine were applied as standard AEDs. Seizure parameters and lethality were recorded in treated animals. Significantly increased latency to seizure onset (insert time), reduced seizure frequency, severity, and lethality in animal models induced by picrotoxin, strychnine, caffeine, and MES. Its efficacy was comparable to the action of reference drugs or exceeded their effects. However, no protective effect of Les-3384 was observed in thiosemicarbazide and camphor models. Molecular docking studies revealed high binding affinity of Les-3384 to the GABAA-receptor, suggesting that GABAergic modulation is a possible mechanism of action. The high effectiveness of Les-3384 in the models of strychnine-induced and caffeine-induced seizures is confirmed by the results of molecular modeling, which indicate the affinity of the studied compound toward glycine and adenosine receptors. The LD50 of Les-3384 for mice is 1208 mg/kg by intragastric administration. The compound's efficacy and safety profile support its further preclinical study as a potential antiepileptic agent with the polytropic mechanisms of action.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148373978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sertraline Has Anticancer Effects and Enhances the Cytotoxicity of Chemotherapeutic Agents Against Pancreatic Cancer Cells 舍曲林具有抗癌作用并增强化疗药物对胰腺癌细胞的细胞毒性。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-07-03 DOI: 10.1002/ardp.70290

Maedeh Shahrabi, Asma Aliparast, Fatemeh Moosavi, Amirsajad Jafari, Negar Firouzabadi, Omidreza Firuzi

{"title":"Sertraline Has Anticancer Effects and Enhances the Cytotoxicity of Chemotherapeutic Agents Against Pancreatic Cancer Cells","authors":"Maedeh Shahrabi, Asma Aliparast, Fatemeh Moosavi, Amirsajad Jafari, Negar Firouzabadi, Omidreza Firuzi","doi":"10.1002/ardp.70290","DOIUrl":"10.1002/ardp.70290","url":null,"abstract":"<div>\u0000 \u0000 Sertraline, a serotonin reuptake inhibitor (SSRI), has been implicated as a drug with repurposing capacities in cancer. This study aimed to evaluate the anticancer efficacy of sertraline alone and in combination with chemotherapeutic agents against pancreatic ductal adenocarcinoma (PDAC) cells. Antiproliferative effects of sertraline and chemotherapeutic agents against SUIT-2, AsPC-1, and MIA-PaCa-2 PDAC cells, either alone or in combination, were determined by MTT assay. Synergistic combinations were further evaluated by clonogenic assays, cell cycle analysis, and Hoechst 33258 apoptosis staining. Reactive oxygen species (ROS) levels were quantified using the DCFH-DA assay. Sertraline exhibited antiproliferative activity against PDAC cells (IC50 = 8.3–16.4 µM). When combined with gemcitabine or mitoxantrone, synergistic cytotoxicity was observed in most cell lines; however, the sertraline–gemcitabine combination demonstrated an additive effect in MIA-PaCa-2 cells. Mean CI values of 0.54 ± 0.06 and 0.80 ± 0.03 in SUIT-2 cells, 0.81 ± 0.04 and 0.79 ± 0.06 in AsPC-1 cells, and 1.06 ± 0.05 and 0.79 ± 0.05 in MIA-PaCa-2 cells, respectively. These combinations suppressed colony formation, altered the cell cycle, and enhanced apoptosis. Additionally, increased ROS generation was observed, particularly in the sertraline–gemcitabine combination, suggesting that oxidative stress may contribute to this interaction. Combinations with doxorubicin or cisplatin did not lead to synergism. These findings provide a rationale for further investigation of sertraline-based combination strategies in pancreatic cancer.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148373959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chaperone-Mediated Autophagy-Directed Degradation of PI3K in Tumor Cells: Development of Multifunctional Peptide-Drug Conjugates With Enhanced Penetration and Selectivity 肿瘤细胞中伴侣介导的自噬定向PI3K降解：具有增强穿透性和选择性的多功能肽-药物偶联物的开发。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-07-03 DOI: 10.1002/ardp.70289

Chenyu Zhang, Honglan Zhong, Xiang Li, Zhenjian Xing, Jiaqi Liu, Rui Yu, Xin Deng

{"title":"Chaperone-Mediated Autophagy-Directed Degradation of PI3K in Tumor Cells: Development of Multifunctional Peptide-Drug Conjugates With Enhanced Penetration and Selectivity","authors":"Chenyu Zhang, Honglan Zhong, Xiang Li, Zhenjian Xing, Jiaqi Liu, Rui Yu, Xin Deng","doi":"10.1002/ardp.70289","DOIUrl":"10.1002/ardp.70289","url":null,"abstract":"<div>\u0000 \u0000 The phosphatidylinositol 3-kinase (PI3K) pathway is frequently hyperactivated in cancers, promoting tumor growth and resistance to conventional therapies. Conventional PI3K inhibitors often suffer from poor tumor selectivity, systemic toxicity, and the development of acquired resistance. To overcome these issues, we have designed multifunctional peptide-drug conjugates (PDCs) utilizing chaperone-mediated autophagy (CMA), a selective lysosomal degradation mechanism, for precise targeting of PI3K. Our approach began with the development of a lead compound, CC-3, derived from Copanlisib and incorporating a CMA-recognition motif (KFERQ-like sequence). We further enhanced this compound by creating TCCC-1, integrating a tumor-homing peptide (Thx) and a cell-penetrating peptide (T2) to improve cellular uptake and specificity. In vitro studies revealed that TCCC-1 effectively induced PI3K degradation, inhibited downstream pAkt signaling, and promoted apoptosis alongside G2/M cell cycle arrest in non-small cell lung cancer (NSCLC) cells, including those resistant to Copanlisib. In vivo experiments using NCI-H460 xenograft models demonstrated that TCCC-1 achieved up to 97.0% tumor suppression at high doses, surpassing the efficacy of Copanlisib, without causing significant systemic toxicity, organ damage, or metabolic disturbances such as hyperglycemia. These results highlight TCCC-1 as a promising therapeutic candidate that leverages CMA for precise PI3K degradation, offering enhanced penetration and selectivity against tumors.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From Retigabine to Azetukalner: Reviving Voltage-Gated Potassium Channels for Epilepsy Therapy 从雷沙滨到阿泽妥卡那：恢复电压门控钾通道用于癫痫治疗。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-07-03 DOI: 10.1002/ardp.70279

Pascal Rosendahl, Lukas Schulig, Andreas Link

{"title":"From Retigabine to Azetukalner: Reviving Voltage-Gated Potassium Channels for Epilepsy Therapy","authors":"Pascal Rosendahl, Lukas Schulig, Andreas Link","doi":"10.1002/ardp.70279","DOIUrl":"10.1002/ardp.70279","url":null,"abstract":"Heterotetrameric KV7.2/3 potassium channels were retrospectively identified as the target of the analgesic flupirtine and the antiepileptic retigabine (ezogabine). Clinical utility of these agents ended after decades or 6 years, respectively, before their full scope was explored. Market withdrawals in 2017 and 2018 hampered research in other medical fields and left a gap for researchers using these compounds off-label in experimental indications and for patients with KV7.2/3 malfunctions. Failure of these drugs might be regarded as a reason to abandon this class of compounds, due to the notion that toxicity might be a class effect and to competitive markets. Yet, evidence accumulated that the toxicity of both compounds is not an inherent property of modulators of KV7.2/3 channels, but rather the result of an oxidation-sensitive metabophore/toxicophore. Second, epilepsy associated with KV7.2/3 channelopathies might rationally be addressed best with modulators of this validated drug target. Employing retrometabolic drug design to remodel the enzyme-labile carbamate structure and the central highly substituted ring, azetukalner (formerly encukalner, XEN1101) emerged from the unlucky forerunners. This structural analog of retigabine exhibits improved metabolic stability, increased potency, and enhanced blood–brain barrier penetration compared with its predecessor. This review details the synthesis, physicochemical properties, and clinical results of azetukalner.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

USFDA-Approved Small Molecules in the Year 2025: Medicinal Chemistry Strategies and Trends 2025年美国fda批准的小分子：药物化学策略和趋势。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-06-15 DOI: 10.1002/ardp.70272

Madhuri P. Rao, Razique Anwer, Sangeeta Benni, M. Arockia Babu, Thakur Gurjeet Singh, Saif Ahmed, Mohammad Fareed, Nisha Bansal

{"title":"USFDA-Approved Small Molecules in the Year 2025: Medicinal Chemistry Strategies and Trends","authors":"Madhuri P. Rao, Razique Anwer, Sangeeta Benni, M. Arockia Babu, Thakur Gurjeet Singh, Saif Ahmed, Mohammad Fareed, Nisha Bansal","doi":"10.1002/ardp.70272","DOIUrl":"10.1002/ardp.70272","url":null,"abstract":"<div>\u0000 \u0000 Small-molecule-based therapeutics play a vital role in drug discovery. These molecules are preferred owing to their oral bioavailability, ease of tuning the physicochemical properties, and broad target accessibility. In this review article, we have explored the small molecules approved by the US Food and Drug Administration (USFDA) in 2025. Through the analysis, we found 44 drug approvals, out of which 30 candidates were approved as new molecular entities (NMEs), while the remaining 14 were approved in the category of biologics, including 10 approved as biosimilars. Considering the therapeutic area distribution of 30 NMEs, 28 drugs are approved as monotherapy, with 10 drugs as anticancer agents, 4 drugs for genetic disorders, 2 drugs each for the conditions of immunological, respiratory, ophthalmic, and endocrine disorders, along with the treatment of cardiac and infectious diseases. The structural diversity analysis revealed that 29 approved drugs were aromatic (azaheterocycles) in nature, and 13 drugs possess at least one stereogenic center. Considering the elemental diversity, the near-universal presence of nitrogen in the form of amines, amides, and as a heteroatom, followed by the oxygen atom. Additionally, the prevalence of 3- or 4-membered carbocyclic or heterocyclic rings was found in five approved drugs. For metabolism, most drugs rely on CYP3A-mediated metabolism, primarily through CYP3A4, CYP2D6, and CYP2C8. Collectively, the analysis and compilation of the drugs presented are expected to provide practical insights and offer guidance to medicinal chemists, biologists, and scientists associated with current drug-discovery paradigms, making continuous strides for future medicinal chemistry innovations and evolutions.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cholesterol and Cholesterol-Derived Molecules Differentially Modulate Neuronal Kv7.2/7.3 Channels 胆固醇和胆固醇衍生分子对神经元Kv7.2/7.3通道的差异调节

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-06-15 DOI: 10.1002/ardp.70280

Elif Karabatak, Ronewa Nematswerani, Vivian Meiritz, Nicole Rychlik, Guiscard Seebohm, Frank Glorius, Thomas Budde

{"title":"Cholesterol and Cholesterol-Derived Molecules Differentially Modulate Neuronal Kv7.2/7.3 Channels","authors":"Elif Karabatak, Ronewa Nematswerani, Vivian Meiritz, Nicole Rychlik, Guiscard Seebohm, Frank Glorius, Thomas Budde","doi":"10.1002/ardp.70280","DOIUrl":"10.1002/ardp.70280","url":null,"abstract":"Kv7 potassium channels generate slowly activating, non-inactivating outward potassium currents and are critical regulators of cellular excitability. While cholesterol is known to modulate multiple ion channels, its concentration-dependent effects and the influence of cholesterol-derived molecules on Kv7 channels remain insufficiently characterized. In this study, we investigated the effects of cholesterol and cholesterol-derived molecules, including steroid hormones and chemically modified imidazolium-based cholesterol derivatives (CHIMs) on Kv7.2/7.3 channels heterologously expressed in HEK293FT cells using conventional whole-cell patch-clamp recordings. Application of high cholesterol concentrations (1 mM) significantly reduced Kv7.2/7.3 current amplitudes over a wide range of potentials without changing voltage-dependent current characteristics. CHIMs also reduced currents, whereas a fluorescent derivative, CHIM-L-NBD, unexpectedly enhanced Kv7.2/7.3 currents. In contrast, the NBD moiety alone had no effect. Progesterone and 17β-estradiol inhibition of Kv7.2/7.3 currents was most evident at strongly depolarized potentials. For progesterone this was associated with a change in the slope of the activation curve. These findings demonstrate that Kv7.2/7.3 channels respond differentially to structural modifications of cholesterol and to steroid hormones thereby suggesting that different cholesterol-derived molecules may serve as tool compounds with potentially opposing modulatory effects on Kv7.2/7.3 channels.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Triazole–Sulfonamide Hybrids as Carbonic Anhydrase Inhibitors: Emerging Chemistry and Bioactivity Insights From 2020 to 2025 三唑-磺胺杂化物作为碳酸酐酶抑制剂：从2020年到2025年的新兴化学和生物活性见解。

IF 3.5 3区医学

Archiv der Pharmazie Pub Date : 2026-06-15 DOI: 10.1002/ardp.70269

Mohamed S. Nafie, Heba F. Ashour, Sherif Ahsraf Fahmy, Mohamed K. Diab, Mohamed Reda Aouad, Nadjet Rezki, Asmaa S. A. Yassen

{"title":"Triazole–Sulfonamide Hybrids as Carbonic Anhydrase Inhibitors: Emerging Chemistry and Bioactivity Insights From 2020 to 2025","authors":"Mohamed S. Nafie, Heba F. Ashour, Sherif Ahsraf Fahmy, Mohamed K. Diab, Mohamed Reda Aouad, Nadjet Rezki, Asmaa S. A. Yassen","doi":"10.1002/ardp.70269","DOIUrl":"10.1002/ardp.70269","url":null,"abstract":"<div>\u0000 \u0000 The development of triazole–sulfonamide hybrids is an emerging frontier in medicinal chemistry, combining the clinically validated sulfonamide core with a triazole linker. This structural synergy has yielded potent and selective carbonic anhydrase inhibitors (CAIs) targeting various human and mycobacterial isoforms. Besides CA inhibition, these hybrids also exhibit multi-target binding. They can also interact with vascular endothelial growth factor receptor-2 (VEGFR-2), telomerase, and other oncological and microbial targets, highlighting their broader therapeutic potential against cancer, tuberculosis, and neuropathic diseases. This review provides an overview of synthetic methods, structure–activity relationships (SAR), and isoform selectivity of triazole–sulfonamide conjugates reported from 2020 to 2025. Unlike other reviews focused on CA inhibitory properties, we highlight the multi-inhibitor pharmacological profile of these hybrids and demonstrate their applications in multi-target drug design.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Channel Dysfunction as the Basis for Comorbidities in Multiple Sclerosis and Depression 经络功能障碍是多发性硬化和抑郁症合并症的基础。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-06-09 DOI: 10.1002/ardp.70273

Nicole Rychlik, Kay Jüngling, Sven G. Meuth, Thomas Budde, Marta Méndez-Couz

{"title":"Channel Dysfunction as the Basis for Comorbidities in Multiple Sclerosis and Depression","authors":"Nicole Rychlik, Kay Jüngling, Sven G. Meuth, Thomas Budde, Marta Méndez-Couz","doi":"10.1002/ardp.70273","DOIUrl":"10.1002/ardp.70273","url":null,"abstract":"Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that is frequently accompanied by major depressive symptoms, which substantially worsen disease burden and quality of life. Increasing evidence suggests that this comorbidity is not solely a psychological reaction to neurological disability but may arise from shared neurobiological mechanisms. Ion channels play a central role in regulating neuronal excitability, synaptic transmission and immune cell function, and their dysregulation has emerged as a key feature of MS pathology. Demyelination and neuroinflammation induce profound alterations in the expression, distribution and function of several ion channel families, including hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, voltage-gated potassium channels such as Kv7 and two-pore domain potassium (K2P) channels. These changes contribute to neuronal hyperexcitability, altered thalamocortical network activity and immune cell activation. Importantly, several ion channel systems implicated in MS are also associated with affective regulation, including TRPA1, ASIC1a, N-methyl-d-aspartate receptors and serotonin 5-HT3 receptors. This review summarizes current evidence linking ion channel dysfunction to both MS pathology and depression and highlights emerging pharmacological strategies targeting these channels. Understanding ion channel-mediated mechanisms may provide novel therapeutic opportunities to address both neuroinflammation and neuropsychiatric comorbidities in MS.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70273","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kv7 and K2P Potassium Channels in Thalamocortical Function and Their Therapeutic Potential in Childhood Absence Epilepsy Kv7和K2P钾通道在丘脑皮质功能中的作用及其对儿童癫痫的治疗潜力。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-06-09 DOI: 10.1002/ardp.70276

Anushka Takhi, Guiscard Seebohm, Thomas Budde, Annika Lüttjohann

{"title":"Kv7 and K2P Potassium Channels in Thalamocortical Function and Their Therapeutic Potential in Childhood Absence Epilepsy","authors":"Anushka Takhi, Guiscard Seebohm, Thomas Budde, Annika Lüttjohann","doi":"10.1002/ardp.70276","DOIUrl":"10.1002/ardp.70276","url":null,"abstract":"Potassium (K+) channels are one of the key regulators of neuronal excitability and network stability. Among all the potassium channels, the voltage-gated Kv7 (KCNQ) and the two-pore domain potassium (K2P) channels play an important role in stabilizing and maintaining the resting potential of neurons. They are involved in controlling the input resistance and in the generation of rhythmic activity in the thalamocortical network. The main functions of the thalamocortical system are the regulation of sensory processing and the generation of brain rhythms underlying sleep and wakefulness. By this, it is essential to many aspects of cognition. The thalamocortical system is explicitly sensitive to fine changes in potassium conductance. The dysregulation of thalamocortical oscillation, also known as thalamocortical dysrhythmia, has been known to be involved in several psychiatric and neurological disorders. A prototypical thalamocortical dysrhythmia is childhood absence epilepsy (CAE), in which hypersynchronous activity in the form of spike and wave discharges (SWD) induces sudden losses of conscious awareness in patients. This review will summarize the current knowledge on Kv7 and K2P channels in the regulation of synchrony and excitability in the brain and the thalamocortical system in particular, outlining future research directions, highlighting the therapeutic potential of these channels for the treatment of thalamocortical dysrhythmias in general and CAE specifically.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70276","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sustainable RP-HPLC Method Development for Simultaneous Estimation of Fampridine and Monomethyl Fumarate in Lipid Nanocarriers and Biological Fluids: Application of AQbd Principles 同时测定脂质纳米载体和生物流体中福必定和富马酸单甲基的可持续RP-HPLC方法的开发：AQbd原理的应用。

IF 3.6 3区医学

Archiv der Pharmazie Pub Date : 2026-06-05 DOI: 10.1002/ardp.70274

Atith Muppayyanamath, Vinayak Mastiholimath

{"title":"Sustainable RP-HPLC Method Development for Simultaneous Estimation of Fampridine and Monomethyl Fumarate in Lipid Nanocarriers and Biological Fluids: Application of AQbd Principles","authors":"Atith Muppayyanamath, Vinayak Mastiholimath","doi":"10.1002/ardp.70274","DOIUrl":"10.1002/ardp.70274","url":null,"abstract":"<div>\u0000 \u0000 Analytical quality by design (AQbD) provides a systematic framework for developing reliable pharmaceutical analytical methods. In this study, environmentally conscious RP-HPLC method was developed for fampridine and monomethyl fumarate, two disease-modifying agents used in multiple sclerosis therapy. Critical risks were mapped by Fishbone diagram, prioritized by ranking and filtering, screened via Taguchi design, and optimized using Box–Behnken design to evaluate the influence of organic phase concentration, flow rate, and column temperature on critical chromatographic responses, namely retention time, tailing factor, and theoretical plates for both fampridine and monomethyl fumarate. Seventeen experimental trials identified optimal conditions consisting of a mobile phase of water with 0.1% ortho phosphoric acid and methanol (85:15% v/v), a flow rate of 1.0 mL/min, column temperature of 35°C, and a Phenomenex Luna C18 column (5 µm, 150 × 4.6 mm). Under these settings, retention times were 3.492 min for fampridine and 9.482 min for monomethyl fumarate. The method demonstrated excellent linearity across 2–12 µg/mL (R2 = 0.9992 for fampridine; R2 = 0.9989 for monomethyl fumarate), with low detection and quantification limits. Recovery studies from lipid nanocarriers yielded values between 96.13% and 98.75%. Forced degradation experiments confirmed sensitivity to acidic, oxidative, and thermal stress, while application to biological matrices produced recoveries above 95%, underscoring bioanalytical applicability.</div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148161023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0