Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Bioequivalence of cefdinir dispersible tablets in healthy Chinese subjects under fasting and fed conditions: a single-centred, randomized, open, single-dose, two-preparation, two-cycle, two-sequence, double-crossover trial.","authors":"Nan Mao, Zuoheng Xu, Jianfen Su, Bingna Wang, Jiajing Xia, Diqun Zheng, Jianxing Liao, Xiaoyan Liu","doi":"10.1007/s00210-024-03701-8","DOIUrl":"https://doi.org/10.1007/s00210-024-03701-8","url":null,"abstract":"<p><p>Cefdinir is a broad-spectrum antibiotic with good antibacterial activity against gram-positive and gram-negative bacteria and can be used for the treatment of various sensitive bacterial infections, such as community-acquired pneumonia, urinary tract infection and gonorrhoea. Herein, a single-centred, randomized, open, single-dose, two-preparation, two-cycle, two-sequence, double-crossover trial with a 7-day washout was conducted to investigate the pharmacokinetics, bioequivalence and safety of cefdinir dispersible tablets and the reference formulation of cefdinir capsules in healthy Chinese volunteers. Fifty-six healthy subjects were recruited and randomly assigned to the fasting and fed groups. After a single oral dose of the test or reference formulation (0.1 g), the cefdinir concentrations in the plasma were determined via HPLC-MS/MS, and pharmacokinetic parameters were obtained from the concentration‒time profiles. Overall, 24 and 31 individuals completed the evaluation under fasting and fed conditions respectively. The mean concentration‒time profiles for both formulations were similar, and the C_max, AUC_0-t and AUC_0-∞ values were entirely within the bioequivalence range of 80.00% to 125.00%. Three subjects reported 5 AEs, and 8 subjects experienced 13 AEs in the fasting and fed groups respectively, but no participants withdrew from the trial because of AEs. All adverse reactions were grade I in severity, and no serious AEs or deaths occurred. The results demonstrated that these formulations were bioequivalent in healthy Chinese subjects under fasting and fed conditions, supporting the further clinical development of cefdinir dispersible tablets. This trial was registered in the China Drug Trials Registry (registration number: CTR20210441; registration date: March 11, 2021).</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory activity of metoclopramide HCl on murine macrophages.","authors":"Esra Aydemir","doi":"10.1007/s00210-024-03715-2","DOIUrl":"https://doi.org/10.1007/s00210-024-03715-2","url":null,"abstract":"<p><p>Metoclopramide HCl is the active ingredient of the commonly used drugs against nausea, heartburn, and acid reflux. Other than the patients with the acid reflux and stomach problems, it has been widely used in patients going through chemotherapy and radiotherapy, as well as patients suffering from migraine with stomach issues. To our knowledge, the immunomodulatory effect of metoclopramide HCl has never been tested extensively. Since patients who are going through chemotherapy and radiotherapy are prone to developing immunodeficiencies, it is imperative to analyze the activity of this active drug ingredient on the mammalian macrophages. For this purpose, the mammalian macrophages were tested for their potential to produce the pro-inflammatory cytokines, in vitro, in the presence and absence of LPS as the stimulating agent with a range of metoclopramide concentrations. Our results suggest that metoclopramide HCl did not stimulate the macrophages by itself; but in the presence of LPS stimulation, it significantly and substantially decreased the production of the pro-inflammatory TNFα, IL-6, GMCSF, and IL12p40 cytokines. Although this study involved solely in vitro model, the results imply that in the clinical setting metoclopramide HCl might induce inflammatory reaction against potential infections.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testicular weight deficits, altered variables of antioxidant defense system, spermatogenesis impairment, and inflammation induced by busulfan injection are ameliorated by gallic acid administration in rats.","authors":"Sunny O Abarikwu, Chinedu J Okonkwo, Ogechukwu E Ezim, Victoria C Obinna, Chisom E Nebeolisa, Lauritta C Ndufeiya-Kumasi","doi":"10.1007/s00210-024-03699-z","DOIUrl":"https://doi.org/10.1007/s00210-024-03699-z","url":null,"abstract":"<p><p>This study evaluated the long-term protective effect of gallic acid (GAL) against testicular lesions induced by busulfan (BUSLF) in Wistar rats. Thirty (30) male rats weighing 60-70 g were randomized into three groups of ten in each group: control (2 ml kg^-1 body weight (b.w) olive oil), BUSLF (10 mg kg^-1 b.w), and BUSLF + GAL (10 mg kg^-1 b.w BUSLF + 20 mg kg^-1 b.w GAL). BUSLF was injected (intraperitoneally) concurrently with GAL (oral gavage) on day 1 but GAL administration continues for 12 weeks in the BUSLF + GAL animals. At the end of the study, all animals did not show relevant changes in body weights, but absolute testis weight and gonado-somatic index were decreased in the BUSLF-treated animals compared to the control values (p < 0.05). These biometric data remained unchanged in the BUSLF + GAL group relative to the control but were higher than the BUSLF values (p < 0.05). GAL co-treatment counteracted BUSLF-induced decrease in glutathione peroxidase activity and an increase in hydrogen peroxide, malondialdehyde, and carbonyl protein concentrations in the testis. Changes in testicular sorbitol and lactate dehydrogenases and myeloperoxidase activities in BUSLF-treated animals were ameliorated in the BUSLF + GAL-treated animals. GAL co-treatment also prevented BUSLF-induced decrease in testosterone and sialic acid concentrations and sperm quality. The spermatogenesis score index and histological changes induced by BUSLF were also abated in the BUSLF + GAL group. GAL has been established as an effective treatment regimen for the gonadal side effects of BUSLF in a rat model.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loc646329 sponges miR-21 to reduce RAS/MAP kinase signaling pathway in oral squamous cell carcinoma (OSCC).","authors":"Akhtar Adereh, Parya Amini, Azadeh Fateh, Ferdos Faghihkhorasani, Nastaran Khdakarim, Seyed Mehdi Marashi, Shana Ahadi, Parnian Nayebzadeh, Amir Khanmirzaei","doi":"10.1007/s00210-024-03671-x","DOIUrl":"https://doi.org/10.1007/s00210-024-03671-x","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive form of head and neck cancer. Emerging evidence suggests that microRNAs (miRNAs) play a crucial role in the development and progression of OSCC. In particular, miR-21 has been implicated in various cellular processes, including proliferation, apoptosis, and invasion; it could be a potential therapeutic target for OSCC. In this study, The Cancer Genome Atlas (TCGA) for OSCC (TCGA-OSCC) clinical information was used. Patient outcomes were analyzed through survival analysis using Kaplan-Meier curves and log-rank tests. The HSC-3cell line was used as the OSCC cell line, which is known for its aggressive characteristics. The expression of Loc646329, miR-21, PTEN, PDCD4, and SPRY2 was evaluated by RT-PCR, flow cytometry, and scratch assay. Also, the effect of Loc646329 expression on OSCC was evaluated using the in vivo Xenograft Mouse Model. The results showed that overexpression of Loc646329 leads to the downregulation of miR-21, PDCD4, and SPRY2 genes while the PTEN gene is upregulated. In other words, the overexpression of Loc646329 by miR-21 inhibition (thorough targeting RAS/MAPK pathway) induces apoptosis and stops the cell cycle in OSCC cells. In vivo tests showed that elevated Loc646329 expression was linked to positive pathological outcomes, such as smaller tumor size, reduced lymph node metastasis, and enhanced overall survival in OSCC patients. In conclusion, the identification of Loc646329 as a sponge for miR-21 and its impact on the RAS/MAPK signaling pathway offers new opportunities for the development of innovative therapeutic strategies for OSCC. Further investigations into this regulatory axis may uncover additional targets for precision medicine approaches in the treatment of OSCC.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piperazine ferulate impact on diabetes-induced testicular dysfunction: unveiling genetic insights, MAPK/ERK/JNK pathways, and TGF-β signaling.","authors":"Basel A Abdel-Wahab, Ehab A M El-Shoura, Mohammed S Habeeb, Nayef A Aldabaan, Yasmine H Ahmed, Dalia Zaafar","doi":"10.1007/s00210-024-03654-y","DOIUrl":"https://doi.org/10.1007/s00210-024-03654-y","url":null,"abstract":"<p><p>Diabetic testicular dysfunction (DTD) poses a significant threat to male reproductive health. This study delves into the potential of piperazine ferulate (PF), a natural phenolic compound, in alleviating DTD and sheds light on its underlying mechanisms in rats. Animals were divided into the control, PF, diabetic, and diabetic plus PF groups. Diabetes was induced in rats with a single intraperitoneal (i.p.) injection of streptozotocin (STZ) at 50 mg/kg. PF was administered at 50 mg/kg/day via i.p. injection for four weeks. Significant changes in sexual behavior were observed in diabetic rats, which additionally revealed lower serum levels of testosterone, FSH, and LH. The abnormalities in sperm count, viability, motility, and morphology occurred along with the demonstrated suppression of genes and protein expression related to spermatogenesis. Atrophy of the seminiferous tubules and extensive degeneration and necrosis of the germ and Leydig cells were highlighted by histopathological examination. The testicular function of diabetic rats was significantly improved after PF administration, evidenced by normalized testicular histology, increased testosterone levels, and enhanced sperm quality. In addition to reducing inflammatory cytokines, COX2, and NF-κB expression, pf administration elevated the antioxidant levels and Nrf2/HO-1 expression. Furthermore, key signaling pathways involved in testicular degeneration are regulated by PF. It promoted cell survival and tissue repair by activating the protective TGF-β signaling pathway and attenuating the MAPK/ERK/JNK signaling cascade, which in turn reduced inflammation and apoptosis. PF suppressed the expression of INSL3, SPHK1, CD62E, ANGPTL2, and miR-148a-5p, while increasing the expression of testicular genes like HSD17B1, DAZL, and S1P, addressing DTD. This study highlights the potential of PF to restore testicular function and fertility in diabetic males by modulating genetic and signaling pathways.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and in vitro tuning of empagliflozin-containing dissolvable microneedle patch for enhanced transdermal delivery.","authors":"Aqib Javed, Rai Muhammad Sarfraz, Asif Mahmood, Zulcaif Ahmad, Muhammad Rouf Akram, Hira Ijaz, Shammas Ali, Anam Shahzadi","doi":"10.1007/s00210-024-03708-1","DOIUrl":"https://doi.org/10.1007/s00210-024-03708-1","url":null,"abstract":"<p><p>This painless method allows drugs to penetrate the outer skin layer, offering several advantages over alternative administration routes, including ease of use and the ability to bypass enterohepatic circulation. Among transdermal drug delivery systems (TDDS), microneedle patches (MNPs) are emerging as an innovative approach for minimally invasive drug delivery, enhancing the skin permeation of substances ranging from macro to micro sizes. This study explores dissolvable microneedle patches (dMNPs) as a novel method to improve the systemic delivery of empagliflozin, an SGLT-2 inhibitor, commonly used to manage type 2 diabetes mellitus (T2DM). However, its oral administration poses challenges due to rapid absorption, variable bioavailability, and a moderate half-life that necessitates frequent dosing. The microneedle patches were manufactured using a mold-based solvent casting technique, utilizing a polymer-drug combination that dissolves upon skin application. The development of the dMNPs involved polyvinylpyrrolidone and polyvinyl alcohol. Characterization of the formulated dMNPs included scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD), dissolution testing, tensile strength analysis, percentage elongation measurement, mechanical strength assessment, and skin irritation studies. The optimized dMNP formulation (MP6) exhibited notable characteristics such as sharp, uniform, pyramid-shaped needles, stability at elevated temperatures, crystalline structures of the drug and polymers, controlled weight loss upon heating, effective drug dissolution, optimal tensile strength, penetration depth, moisture content, elongation capability, and a favorable release rate. In vitro release demonstrated the enhanced properties of the dissolvable microneedle patches, with zero-order kinetics identified as the most suitable model for MP6 based on regression coefficient analysis. Overall, the characterization studies, in vitro skin irritation evaluation, confirmed the stability and biocompatibility of the optimized dMNPs, making them suitable for transdermal application.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhazes' insights on abortion and abortogenic drugs in relation to modern concepts.","authors":"Mohammad Amrollahi-Sharifabadi, Jamal Rezaei Orimi, Syed Mohd Abbas Zaidi, Toheeb Olalekan Oladejo, Abdur Rahman, Sageer Abass, Sayeed Ahmad, Sahar Abdelaziz, Mohammad Bahrami-Tapehbour, Marwa M M Fawzy, Morteza Mojahedi","doi":"10.1007/s00210-024-03698-0","DOIUrl":"https://doi.org/10.1007/s00210-024-03698-0","url":null,"abstract":"<p><p>Abortion remains one of the most prevalent complications of pregnancy, contributing significantly to maternal mortality and presenting a substantial public health challenge. This study aimed to explore Rhazes' perspective on abortion and abortifacient medicinal plants he mentioned in Kitāb al-Ḥāwī fī al-Ṭibb. A detailed analysis of his seminal work, Kitāb al-Ḥāwī fī al-Ṭibb, was conducted. Relevant keywords such as abortion, stillbirth, fetus, drugs, and abortifacients were examined within Kitāb al-Ḥāwī fī al-Ṭibb. The analysis included Rhazes' viewpoints on abortion and the abortogenic drugs he mentioned, as well as their methods of administration, including oral dosage forms and vaginal formulations. Furthermore, relevant current literature was used to find the potential scientific rationales for Rhazes' insights. Our findings indicate that Rhazes contributed to obstetrics and gynecology as he discussed abortion, its prevention, and management in his book. Also, he identified various medicinal plants with potential abortogenic properties. Rhazes explained various administration methods, including rub, decoction, inhalation, suppository, enema, incense, and water bath. Even though his clinical practices and detailed observations provide a rich context for understanding the historical use of these agents, evidence-based medical practices need to be conducted to cleave potentially usable parts of Rhazes' perspectives and his approaches to the prevention and treatment of abortion. Moreover, there is a pressing need for well-designed randomized clinical trials to rigorously evaluate the potential efficacy and safety of the medical insights and the potential therapeutic herbal agents he described.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of platinum nanoparticles functionalized with glutamine and conjugated with thiosemicarbazone and their cytotoxic effects on MDA-MB-231 breast cancer cell line and evaluation of CASP-8 gene expression.","authors":"Nabeel Rahi Mashkoor, Salwan Ali Abed, Arash Davoudi, Zahraa Aqeel Adel Jassim, Zainab Yousif Faraj, Fatemeh Akbari, Fahimeh Abedini Bajgiran, Mohammad Hedayati, Ali Salehzadeh","doi":"10.1007/s00210-024-03629-z","DOIUrl":"https://doi.org/10.1007/s00210-024-03629-z","url":null,"abstract":"<p><p>Breast cancer (BC) is the most prevalent form of cancer among women and is a major contributor to cancer-related fatalities. Nanotechnology has provided novel approaches to drug delivery to cancer cells. In this work, we synthesized platinum (Pt) nanoparticles, functionalized them with glutamine, conjugated them with thiosemicarbazone (TSC), and characterized their anticancer effects on the MDA-MB-231 breast cancer cell line. Characteristics of the nanoparticles were assessed by FT-IR, XRD, EDS mapping, SEM, TEM, DLS, and zeta potential measurement. Cell viability was characterized by MTT assay, and cell necrosis/apoptosis levels were determined by flow cytometry. The expression level of the CASP-8 gene was investigated by real-time PCR. Pt@Gln-TSC nanoparticles are spherical, 20-70 nm in diameter in dry form, 662 nm after hydration, and their zeta potential was - 6.6 mV. The 50% inhibitory concentration (IC₅₀) for MDA-MB-231 (breast cancer) and HDF (normal) cell lines was 170 and 348µg/ml, respectively. Also, the IC₅₀ of oxaliplatin drug and TSC on MDA-MB-231 cells was 184 µg/ml and 307 µg/ml, respectively. Treatment with Pt@Gln-TSC nanoparticles caused an increase in cell necrosis and primary apoptosis and elevated the expression of the CASP-8 gene by 2.54 folds. This study shows that Pt@Gln-TSC nanoparticles are significantly more toxic to breast cancer cells than to normal cells and can inhibit MDA-MB-231 cells by activating extrinsic apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalin plays a protective role by regulating ferroptosis in multiple diseases.","authors":"Shiyun Guo, Qi Zhang, Hangwei Ge, Honggang Wang","doi":"10.1007/s00210-024-03704-5","DOIUrl":"https://doi.org/10.1007/s00210-024-03704-5","url":null,"abstract":"<p><p>Ferroptosis is a new kind of cell death discovered in recent years, usually accompanied by a large number of lipid peroxidation and iron accumulation in the process of cell death. Ferroptosis has been proven to play an important role in various diseases, including ischemic reperfusion injury, cancer, and neurodegeneration. Therefore, the regulation of ferroptosis will have a vital impact on the occurrence and development of diseases. Baicalin is a flavonoid compound extracted and isolated from the dried roots of Scutellaria baicalensis Georgi, a plant in the family Lamiaceae. It has various biological activities such as antioxidant, anti-proliferative, anti-inflammatory, anti-thrombotic, and regulates apoptosis and ferroptosis. Recently, increasing evidence indicates that baicalin regulation of ferroptosis is involved in multiple diseases. However, the relevant mechanisms are not yet fully understood. Here, we summarized the role of baicalin regulation of ferroptosis in different kinds of diseases, and conducted an in-depth analysis of the relevant mechanisms, hoping to provide the theoretical references for future related researches.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine is a functional antagonist at cardiac human H₂-histamine receptors.","authors":"Jonas M A Schlicht, Undine Ahlrep, Britt Hofmann, Uwe Kirchhefer, Joachim Neumann, Ulrich Gergs","doi":"10.1007/s00210-024-03683-7","DOIUrl":"https://doi.org/10.1007/s00210-024-03683-7","url":null,"abstract":"<p><p>Clozapine is an atypical antipsychotic (neuroleptic) drug. Clozapine binds to H₂-histamine receptors in vitro. We wanted to test the hypothesis that clozapine might be a functional antagonist at human cardiac H₂-histamine receptors. To that end, we studied isolated electrically stimulated left atrial preparations and spontaneously beating right atrial preparations from transgenic mice with cardiomyocyte-specific overexpression of the human H₂-histamine receptor (H₂-TG). For comparison, we used wild-type littermate mice (WT). Finally, we measured isometric force of contraction in isolated electrically stimulated muscle strips from the human right atrium (HAP) obtained from patients during bypass surgery. After pre-stimulation with histamine, clozapine (up to 10 µM) concentration and time dependently decreased beating rate in right atrial preparations from H₂-TG. Clozapine concentration dependently 1, 3, and 10 µM decreased histamine-stimulated force of contraction in HAP. Clozapine (10 µM) decreased also the isoprenaline-stimulated force of contraction in HAP. In summary, clozapine can antagonize the function of H₂-histamine and β-receptors in the human heart.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}