Article
Neurosciences
Kevin M. Manz, Jennifer C. Becker, Carrie A. Grueter, Brad A. Grueter
Summary: The study reveals that stress-induced histamine signaling in the NAc recruits H-3 heteroreceptor signaling to shift thalamocortical input onto D1(+)-MSNs in the NAc. These findings provide novel insights into an understudied neuromodulatory system within the NAc and implicate histamine in stress-related physiological states.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Immunology
Jiangong Wang, Bin Liu, Fengjiao Sun, Yong Xu, Haiyun Luan, Meizi Yang, Chaoyun Wang, Tiantian Zhang, Zhenyu Zhou, Haijing Yan
Summary: This study found that inhibition of H3R reduced microglia activity and promoted a shift from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype in microglia, thereby attenuating lipopolysaccharide-induced neuroinflammation in mice. Additionally, inhibition of H3R rescued the impairments of neurogenesis and cognitive function caused by neuroinflammation. Mechanistically, the neuroprotective effects of H3R inhibition were mediated by histamine-dependent activation of H2R and reinforcement of CREB-CBP interaction, which led to increased release of anti-inflammatory cytokines and brain-derived neurotrophic factor, as well as decreased release of pro-inflammatory cytokines.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Kamil Mika, Malgorzata Szafarz, Marek Bednarski, Kamil Kuder, Katarzyna Szczepanska, Krzysztof Pociecha, Bartosz Pomierny, Katarzyna Kiec-Kononwicz, Jacek Sapa, Magdalena Kotanska
Summary: The study supports the use of active histamine H3 receptor ligands as new therapeutic agents for treating obesity. Compounds KSK-61 and KSK-63 are considered as leading structures due to their ability to slow weight gain and compensate for metabolic disorders.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Physical
Andrzej Olczak, Jaroslaw Sukiennik, Beata Olszewska, Monika Stefaniak, Krzysztof Walczynski, Malgorzata Szczesio
Summary: Seven new low-temperature structures of 4-n-propylpiperazine derivatives, potential H3 receptor antagonists, have been determined, displaying N-H···Br hydrogen bonding and laying the foundation for the search for new non-imidazole histamine H3 receptor antagonists.
Article
Psychiatry
Yongqian Wang, Xufeng Huang, Hongzhen Fan, Huimei An, Ting Ma, Qi Zhang, Wenxuan Zhao, Yajun Yun, Wenshuang Yang, Xiaolu Zhang, Zhiren Wang, Fude Yang
Summary: This study showed that high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in Chinese Han patients with schizophrenia. Betahistine (72 mg/d) was considered safe for use in these patients.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Behavioral Sciences
Hu Luo, Xiaofang Li, Runyue Fan, Yuer Ruan, Liyin Qian, Yao Shen, Zizhen Si, Longhui Li, Yu Liu
Summary: This study investigated the effect of H3 receptor blockade on METH-induced cognitive impairment and the underlying mechanism. The results showed that METH exposure led to cognitive impairment and hippocampal apoptosis in mice, as well as increased H3 receptor protein levels in HT22 cells. However, treatment with the H3 receptor antagonist THIO improved METH-induced cognitive impairment and toxicity in both mice and HT22 cells. These findings suggest that THIO has a neuroprotective effect against METH-induced cognitive impairment and cell toxicity via the raf-MEK-ERK signaling pathway.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Article
Biochemistry & Molecular Biology
Vittoria Borgonetti, Nicoletta Galeotti
Summary: Growing evidence suggests that the histamine system could be a promising target for the management of neuropathic pain. This study investigated the role of H4R in the anti-hyperalgesic action of the H3R antagonist GSK189254 in a mouse model of spared nerve injury (SNI). The results demonstrate the selective contribution of H4R to the attenuation of hypernociceptive behavior induced by the H3R antagonist, which could help identify innovative therapeutic interventions for neuropathic pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Yousef M. Abdulrazzaq, Salim M. A. Bastaki, Ernest Adeghate
Summary: The human histamine H3 receptor plays a regulatory role in histamine synthesis and release in the brain, affecting processes such as cognition, sleep, and homoeostasis. H3 receptor antagonists have the potential to be important in the treatment of disorders related to cognition, sleep, oxidative stress, inflammation, and glucose homoeostasis.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Clinical Neurology
Luyuan Bai, Weiye Liang, Yongqian Wang, Ning Fan, Qi Zhang, Yun Bian, Fude Yang
Summary: The study investigates the ability of betahistine to inhibit weight gain and abnormal lipid metabolism in patients with chronic schizophrenia. A comparison study was conducted for 4 weeks in 94 patients, where they were randomly divided into two groups receiving either betahistine or placebo therapy. The results show that betahistine may delay metabolic abnormalities in chronic schizophrenia patients, providing new treatment ideas for metabolic syndrome in this population.
NEUROPSYCHIATRIC DISEASE AND TREATMENT
(2023)
Article
Neurosciences
Olga A. Sergeeva, Karolina Mazur, David Reiner-Link, Kiril Lutsenko, Helmut L. Haas, Mercedes Alfonso-Prieto, Holger Stark
Summary: Researchers have found that Nα-oleoylhistamine (OLHA) can modulate the activity of histaminergic (HA) neurons in mice. OLHA has different effects on HA neuron firing depending on its concentration. The excitatory and rise in intracellular calcium caused by OLHA are influenced by specific receptors and inhibitors, possibly related to fatty acid metabolism and the PKA pathway. PPAR-alpha and H3 receptors play important roles in this process.
Article
Neurosciences
Junya Fukuda, Kazunori Matsuda, Go Sato, Tadashi Kitahara, Momoyo Matsuoka, Takahiro Azuma, Yoshiaki Kitamura, Koichi Tomita, Noriaki Takeda
Summary: In this study, betahistine was found to enhance the late process of vestibular compensation in rats after unilateral labyrinthectomy, while having no effect on the initial process. This suggests a potential role for betahistine in facilitating the recovery of vestibular function following inner ear surgery.
Article
Chemistry, Multidisciplinary
Lanchang Gao, Chao Hao, Ru Ma, Jiali Chen, Guisen Zhang, Yin Chen
Summary: In this study, a novel series of multi-receptor ligands were designed and synthesized as polypharmacological antipsychotic agents, among which compound 3w showed high mixed affinities for multiple receptors. Compound 3w demonstrated favorable antipsychotic drug-like activities in in vivo assessment and exhibited low liabilities for weight gain and hyperprolactinemia in a long-term model of metabolic adverse effects. This compound was selected as a candidate for further development as an antipsychotic medication.
Editorial Material
Biochemistry & Molecular Biology
Maarten Dhaenens
Summary: The study investigates histone H4 clipping during intestinal development, offering crucial clues to finally elucidate the intricacies of this elusive modification.
Article
Nutrition & Dietetics
Sonia Sanchez-Perez, Oriol Comas-Baste, M. Teresa Veciana-Nogues, M. Luz Latorre-Moratalla, M. Carmen Vidal-Carou
Summary: A low-histamine diet is currently the most advised strategy for preventing the symptoms of histamine intolerance. However, there is great heterogeneity in the type of excluded foods among different studies, with fermented foods being the only unanimous exclusion. Approximately 32% of excluded foods have high histamine content as a likely explanation.
Article
Chemistry, Multidisciplinary
Ana Borota, Liliana Halip, Ramona Curpan, Alina Bora, Sorin Avram, Maria Mracec, Mircea Mracec
Summary: Theoretical methods and pharmacophore models were used to analyze the structure of histamine H-3 receptor, identifying key binding sites and important amino acids for ligand binding and receptor activation. The models developed can be utilized for virtual screening to identify new potent ligands for the receptor.
STRUCTURAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Ryan M. Wyatt, Ian Fraser, Natalie Welty, Brian Lord, Michelle Wennerholm, Steven Sutton, Michael K. Ameriks, Christine Dugovic, Sujin Yun, Allison White, Leslie Nguyen, Tatiana Koudriakova, Gaochao Tian, Javier Suarez, Lawrence Szewczuk, William Bonnette, Kay Ahn, Brahma Ghosh, Christopher M. Flores, Peter J. Connolly, Bin Zhu, Mark J. Macielag, Michael R. Brandt, Kristen Chevalier, Sui-Po Zhang, Timothy Lovenberg, Pascal Bonaventure
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Bartosz Balana, Jeffrey Schoellerman, Brian Lord, Ryan Wyatt, Jose Matta, Robert Neff, Natalie Welty, Anindya Bhattacharya, Pascal Bonaventure, Tim Lovenberg, Michael Letavic
Meeting Abstract
Biochemistry & Molecular Biology
Jeffrey Schoellerman, Brian Lord, Anindya Bhattacharya, Pascal Bonaventure, Michael Letavic, Tim Lovenberg, Bartosz Balana
Article
Chemistry, Medicinal
Cathy Preville, Pascal Bonaventure, Tatiana Koudriakova, Brian Lord, Diane Nepomuceno, Michele Rizzolio, Neelakandha Mani, Kevin J. Coe, Anthony Ndifor, Christine Dugovic, Curt A. Dvorak, Heather Coate, Daniel J. Pippel, Anne Fitzgerald, Brett Allison, Timothy W. Lovenberg, Nicholas Carruthers, Brock T. Shireman
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Pharmacology & Pharmacy
Lien Wang, Christine Dugovic, Sujin Yun, Allison White, Brian Lord, Curt Dvorak, Changlu Liu, Timothy Lovenberg, Pascal Bonaventure
EUROPEAN JOURNAL OF PHARMACOLOGY
(2020)
Article
Multidisciplinary Sciences
Grace Woodruff, Naomi Phillips, Cassiano Carromeu, Oivin Guicherit, Alistair White, McCay Johnson, Fabian Zanella, Blake Anson, Timothy Lovenberg, Pascal Bonaventure, Anthony W. Harrington
Article
Biochemical Research Methods
Gareth D. Fenn, Helen Waller-Evans, John R. Atack, Benjamin D. Bax
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2020)
Article
Chemistry, Medicinal
Curt A. Dvorak, Dale A. Rudolph, Diane Nepomuceno, Lisa Dvorak, Brian Lord, Ian Fraser, Pascal Bonaventure, Timothy Lovenberg, Nicholas I. Carruthers
Summary: A novel dual 5-HT7/5-HT2 receptor antagonist, 3-(4-Fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydro-1,2,6-triaza-azulene (4j), showed high affinity for both receptors with potential therapeutic efficacy in in vivo models for central 5-HT7 and 5-HT2A activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biology
Chloe R. Koulouris, Sian E. Gardiner, Tessa K. Harris, Karen T. Elvers, S. Mark Roe, Jason A. Gillespie, Simon E. Ward, Olivera Grubisha, Robert A. Nicholls, John R. Atack, Benjamin D. Bax
Summary: Human serine racemase (hSR) catalyzes the conversion of L-serine to D-serine and plays a role in the activation of NMDA receptors. The positioning of Tyr121 appears to be crucial in regulating the activity of hSR.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Anthony W. Harrington, Changlu Liu, Naomi Phillips, Diane Nepomuceno, Chester Kuei, Joseph Chang, Weixuan Chen, Steven W. Sutton, Daniel O'Malley, Ly Pham, Xiang Yao, Siquan Sun, Pascal Bonaventure
Summary: The study suggests that oxysterols, including 24S-HC, could be physiological activators for GPR17, regulating oligodendrocyte progenitor cell differentiation and myelination through receptor activation.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaventure, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
James W. Noble, John R. Atack
Summary: This study investigates the interaction between Calbindin-D28k and IMPase, and reveals that the fusion proteins have higher activity and a different shape compared to the previous model. These findings provide important insights into this protein-protein interaction.
BIOCHEMISTRY AND BIOPHYSICS REPORTS
(2022)
Meeting Abstract
Neurosciences
Benjamin Throesch, Michelle Wennerholm, Pascal Bonaven-Ture, Grace Woodruff
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
Vivien Zell, Pascal Bonaventure, Grace Woodruff, Wayne Drevets, Bartosz Balana
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
Jose Matta, Christine Dugovic, Sujin Yun, Ian Fraser, Daniel Knowland, Weston Davini, Ryan Wyatt, Pascal Bonaventure
NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
