Article
Chemistry, Medicinal
Denise Moennich, Martin Nagl, Lisa Forster, Niklas Rosier, Patrick Igel, Steffen Pockes
Summary: This study reports the synthesis of a new H3R radioligand [H-3]UR-MN259 with high purity and stability, which has high affinity and outstanding selectivity for H3R. The radioligand can be used to investigate the binding characteristics of H3R ligands and shows fast association and dissociation in kinetic binding experiments.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Sabrina Biselli, Merlin Bresinsky, Katharina Tropmann, Lisa Forster, Claudia Honisch, Armin Buschauer, Gunther Bernhardt, Steffen Pockes
Summary: A series of novel H2R and D3R agonists with high affinities and selectivity have been synthesized in this study, showing promising application prospects in in vitro experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Sherin Saheera, Ajay Godwin Potnuri, Ashrith Guha, Suresh S. Palaniyandi, Rajarajan A. Thandavarayan
Summary: Understanding the role of mast cells and histamine in cardiovascular diseases, particularly in cardiac hypertrophy, can lead to better disease management. Research on histamine receptors has shown improvement in cardiac function, suggesting potential for novel therapies in the future.
DRUG DISCOVERY TODAY
(2022)
Article
Cell Biology
Ewelina Honkisz-Orzechowska, Katarzyna Popiolek-Barczyk, Zuzanna Linart, Jadwiga Filipek-Gorzala, Anna Rudnicka, Agata Siwek, Tobias Werner, Holger Stark, Jakub Chwastek, Katarzyna Starowicz, Katarzyna Kiec-Kononowicz, Dorota Lazewska
Summary: This study demonstrates the strong anti-inflammatory effect of new human H3R ligands with flavonoid structure in murine microglial cells. Further research is needed to understand the mechanism of action of flavonoids in reducing inflammation.
INFLAMMATION RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Joachim Neumann, Denise Schwarzer, Charlotte Fehse, Rebecca Schwarz, Margareta Marusakova, Uwe Kirchhefer, Britt Hofmann, Ulrich Gergs
Summary: The study revealed a functional interaction between histamine and serotonin in the heart of double transgenic mice, leading to an impact on cardiac muscle contraction due to the joint overexpression of receptors. Additionally, a similar interaction was found in the muscle fibers of the human right atrium.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Joachim Neumann, Rafaela Voss, Ulrich Laufs, Christian Werner, Ulrich Gergs
Summary: Histamine exerts cAMP-dependent positive inotropic effects (PIE) on the left and right atria of transgenic mice which overexpress the human H-2-receptor, with PDE 3 and PDE 4 regulating the effects on inotropic response, while PDE 2 and PDE 4 play a role in regulating the positive chronotropic effects on heart beat rate.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Anil Karbhari Shinde, Rajesh Kumar Badange, Veena Reballi, Pramod Kumar Achanta, Kumar Bojja, Sravanthi Manchineella, Nageswara Rao Muddana, Ramkumar Subramanian, Raghava Choudary Palacharla, Vijay Benade, Pradeep Jayarajan, Jagadeesh Babu Thentu, Bujji Babu Lingavarapu, Sivasekhar Yarra, Narendra Kagita, Mallikarjuna Rao Doguparthi, Abdul Rasheed Mohammed, Ramakrishna Nirogi
Summary: Compound 45 e, developed through a series of chemical optimizations, has been identified as a potent and selective H3R inverse agonist, with robust efficacy in fighting against dipsogenia induced by histamine. It has shown good oral exposure and half-life, along with significant effects in object recognition task and acetylcholine levels, suggesting potential for further treatment of cognitive disorders associated with Alzheimer's disease.
Review
Chemistry, Medicinal
Joachim Neumann, Britt Hofmann, Uwe Kirchhefer, Stefan Dhein, Ulrich Gergs
Summary: Histamine can affect cardiac contraction force and beating rate in mammals, including humans, but there are significant differences between species and regions. The mammalian heart produces and contains histamine, which may have autocrine or paracrine effects. Cardiomyocytes express histamine receptors, including H-1 and H-2, but their functional role is not fully understood. This review aims to identify gaps in knowledge and highlight the potential of histamine H-1 receptors as therapeutic targets in the human heart, particularly in diseases.
Article
Biochemistry & Molecular Biology
Kamil J. Kuder, Magdalena Kotanska, Katarzyna Szczepanska, Kamil Mika, David Reiner-Link, Holger Stark, Katarzyna Kiec-Kononowicz
Summary: Researchers designed a series of dual acting histamine H-3 receptor ligands, with compound 16 demonstrating strong antioxidant properties and moderate hH(3)R affinity. These compounds could serve as potential tools for treating neurological disorders.
Article
Biochemistry & Molecular Biology
Kamil Mika, Malgorzata Szafarz, Monika Zadrozna, Barbara Nowak, Marek Bednarski, Katarzyna Szczepanska, Krzysztof Pociecha, Monika Kubacka, Noemi Nicosia, Izabela Juda, Katarzyna Kiec-Kononowicz, Magdalena Kotanska
Summary: This study evaluated the activity of two new H3 receptor antagonists, KSK-60 and KSK-74, in reducing weight gain and their impact on metabolic parameters, adipocyte size, and number in a rat model of excessive eating. The compounds also displayed significant affinity at the sigma-2 receptor. The results showed that KSK-74 effectively reduced weight gain, improved metabolic disturbances, and protected against adipocyte hypertrophy and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Steffen Pockes, Katharina Tropmann
Summary: Radioligands have been a powerful tool in investigating the histamine H-2 receptor (H2R) and its functions, with tritium labeling primarily used for in vitro assays and carbon-14 labeling preferred for metabolic studies. The recent development of a G protein-biased radioligand represents a step forward in understanding the potentially unknown role of H2R in the central nervous system through future studies.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Xiaoyi Zhao, Shady Younis, Hui Shi, Shu Hu, Amin Zia, Heidi H. Wong, Eileen E. Elliott, Tiffany Chang, Michelle S. Bloom, Wei Zhang, Xiangyang Liu, Tobias Volker Lanz, Orr Sharpe, Zelda Z. Love, Qian Wang, William H. Robinson
Summary: This study investigated the role of mast cells in osteoarthritis (OA) through RNA-Seq analysis and pharmacological blockade of histamine activity. The findings suggest that mast cells in OA synovium are correlated with disease severity, and inhibiting histamine activity has the potential to improve OA outcome.
CLINICAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kamil Mika, Malgorzata Szafarz, Marek Bednarski, Agata Siwek, Katarzyna Szczepanska, Katarzyna Kiec-Kononowicz, Magdalena Kotanska
Summary: This study evaluated the safety of histamine H-3/sigma-2 receptor ligands by assessing their effects on various parameters. The results showed that the ligands tested at a specific dose did not have negative effects on locomotor activity, motor coordination, cardiac function, blood pressure, and cellular enzymes. These findings suggest that the ligands are safe for further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Shangze Gao, Keyue Liu, Wenhan Ku, Dengli Wang, Hidenori Wake, Handong Qiao, Kiyoshi Teshigawara, Masahiro Nishibori
Summary: Histamine induces the release of HMGB1 from vascular endothelial cells through H-1 receptor stimulation, and anti-HMGB1 therapy may provide a novel treatment for systemic allergies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hayato Akimoto, Minoru Sugihara, Shigeru Hishinuma
Summary: Thermodynamic analyses revealed that Lys179(ECL2) and Lys191(5.39) play different roles in regulating the electrostatic and hydrophobic binding of bilastine to H-1 receptors, reducing its affinity through decreasing enthalpy- and entropy-dependent binding forces, respectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Heiko Schenk, Detlef Neumann, Christina Kloth
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
(2016)
Article
Pharmacology & Pharmacy
Eva J. Wunschel, Bastian Schirmer, Roland Seifert, Detlef Neumann
FRONTIERS IN PHARMACOLOGY
(2017)
Article
Immunology
Bastian Schirmer, Luisa Bringmann, Roland Seifert, Detlef Neumann
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Pharmacology & Pharmacy
Bastian Schirmer, Luisa Lindemann, Kaya Saskia Bittkau, Rukijat Isaev, Daniela Boesche, Malte Juchem, Roland Seifert, Detlef Neumann
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2020)
Article
Geriatrics & Gerontology
Domiziana Costamagna, Robin Duelen, Fabio Penna, Detlef Neumann, Paola Costelli, Maurilio Sampaolesi
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2020)
Article
Oncology
Bastian Schirmer, Tamina Rother, Inga Bruesch, Andre Bleich, Christopher Werlein, Danny Jonigk, Roland Seifert, Detlef Neumann
Review
Biochemistry & Molecular Biology
Bastian Schirmer, Detlef Neumann
Summary: Histamine is a versatile mediator involved in various physiological processes, including the regulation of inflammation. Approved compounds targeting histamine receptors are used for allergic inflammation, gastric acid reduction, and narcolepsy treatment. H4R ligands are still under investigation for inflammatory diseases, showing moderate effects so far.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Pharmacology & Pharmacy
Detlef Neumann, Roland Seifert
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jasper Carsten Schrammel, Martin Koenig, Miriam Frommer, Kaya Saskia Andersen, Marla Kirsten, Roland Seifert, Detlef Neumann, Bastian Schirmer
Summary: By studying cell lines, it was found that colon epithelial cells have functional expression of H4 receptors, which further confirmed the involvement of H4 receptors in inflammatory bowel disease and associated colon cancer. However, the transferability of these data to humans is uncertain. The expression of histamine receptor subtypes varied among different cell lines, and genetic modification is necessary for detailed functional analysis in human colon-derived cell lines.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Meeting Abstract
Cell Biology
T. Rother, B. Schirmer, R. Seifert, D. Neumann
INFLAMMATION RESEARCH
(2019)
Meeting Abstract
Pharmacology & Pharmacy
T. Rother, B. Schirmer, R. Seifert, D. Neumann
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2019)
Meeting Abstract
Cell Biology
D. Neumann
INFLAMMATION RESEARCH
(2018)
Meeting Abstract
Pharmacology & Pharmacy
D. Neumann, E. Wunschel, B. Schirmer
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2017)
Meeting Abstract
Pharmacology & Pharmacy
B. Schirmer, T. Rezniczek, R. Seifert, D. Neumann
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2016)
Meeting Abstract
Pharmacology & Pharmacy
K. Bittkau, L. Bringmann, D. Boesche, R. Isaev, B. Schirmer, R. Seifert, D. Neumann
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2018)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)