Review
Behavioral Sciences
Gabriella E. DiCarlo, Mark T. Wallace
Summary: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and restricted interests/repetitive behaviors. Over 1000 genes and 2000 copy number variants have been implicated in ASD. It is believed that there is not a single genetic cause or neurobiological basis for ASD, but rather multiple subtypes with different genetic and neurobiological perturbations. Dopamine dysfunction may be one potential subtype associated with ASD. This research provides a framework for subcategorizing ASD based on genetic changes, neurobiological differences, and behavioral features.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Gisela Andrea Camacho-Hernandez, Andrea Casiraghi, Deborah Rudin, Dino Luethi, Therese C. Ku, Daryl A. Guthrie, Valentina Straniero, Ermanno Valoti, Gerhard J. Schutz, Harald H. Sitte, Amy Hauck Newman
Summary: The study used fluorescent ligands to investigate the function and distribution of monoamine transporters. By extending SAR for nisoxetine and talopram, high affinity rhodamine-labeled fluorescent probes were identified for the norepinephrine transporter (NET). Nisoxetine-based fluorescent probe 6 showed high binding affinity for NET and stained both NET and SERT in transporter-expressing cells at low concentrations.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hyomin Ahn, Kichul Park, Dongyoung Kim, Sung-Gil Chi, Kee-Hyun Choi, Seo-Jung Han, Chiman Song
Summary: This study examines the pharmacological properties of selective reuptake inhibitors for dopamine, norepinephrine, and serotonin and finds antagonistic effects when they are used in combination. Furthermore, it suggests the presence of a potential secondary inhibitor binding site that affects inhibition.
Article
Biochemistry & Molecular Biology
Marta Pardo, Michele Martin, Raul R. Gainetdinov, Deborah C. Mash, Sari Izenwasser
Summary: This study used a DAT transgenic rat model to investigate the effects of cocaine on locomotor behaviors in adolescent rats. The results showed gender differences in vulnerability to cocaine abuse in adolescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Haelim Jeong, Jun Young Park, Ji-Hyun Lee, Ja-Hyun Baik, Chae-Yeon Kim, Jin-Young Cho, Monica Driscoll, Young-Ki Paik
Summary: The discovery of rcat-1 as a novel negative transcriptional regulator for dopamine metabolism genes has provided insights into the regulation of food search-associated locomotion. The mutants of rcat-1 exhibit abnormal movement behaviors and potential deficiencies in food sensing or locomotion toward food. This finding not only identifies a new subtype of dopamine-related behaviors but also suggests a potential therapeutic target in Parkinson's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Milky Kohno, Laura E. Dennis, Holly McCready, William F. Hoffman
Summary: This review compares the epidemiology of cocaine and methamphetamine use disorder, discusses the effects of drugs on the dopamine system, and summarizes treatment results from pharmacological clinical trials.
MOLECULAR PSYCHIATRY
(2022)
Review
Pharmacology & Pharmacy
Gisela Andrea Camacho-Hernandez, Khorshada Jahan, Amy Hauck Newman
Summary: Fluorescence microscopy has revolutionized the visualization of physiological processes in live-cell systems, and with the recent innovations in super resolution microscopy, these events can be examined with high precision and accuracy. The development of fluorescently labelled small molecules has provided a significant advance in understanding the physiological relevance of targeted proteins that can now be visualized at the cellular level. The study of monoamine transporters (MATs) and their regulation and dysregulation is crucial for treating neuropsychiatric conditions, and the design of fluorescently labelled ligands (FLL) has greatly contributed to advancing our understanding of MATs in health and disease.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jing Deng, Ting Zhang, Xirong Zheng, Linyue Shang, Chang-Guo Zhan, Fang Zheng
Summary: Dysregulation of dopamine transporters due to cocaine exposure leads to a slow recovery process of the dopaminergic system. Acute and repeated cocaine exposures have different impacts on and recovery processes of the dopaminergic system, while a cocaine hydrolase called CocH5-Fc (M6) can effectively protect the dopaminergic system from damage caused by cocaine.
Article
Environmental Sciences
Palanisamy Sivanandy, Tan Choo Leey, Tan Chi Xiang, Tan Chi Ling, Sean Ang Wey Han, Samantha Lia Anak Semilan, Phoon Kok Hong
Summary: Parkinson's Disease (PD) is a neurodegenerative disease characterized by motor and non-motor symptoms. Conventional drugs used for PD have limitations. Safinamide appears to be more efficacious and safer as an adjunct therapy for controlling motor symptoms. A combination of conventional therapy and non-pharmacological treatment is recommended to enhance the well-being of PD patients.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Review
Pharmacology & Pharmacy
Amy Hauck Newman, Therese Ku, Chloe J. Jordan, Alessandro Bonifazi, Zheng-Xiong Xi
Summary: Efforts to develop medications for treating psychostimulant use disorders have not been successful, with potential targets for pharmacotherapies still needing to be identified for future drug development.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Neurosciences
Dakota B. Zinani, Hanna N. Wetzel, Andrew B. Norman
Summary: This study revealed significant differences in the intake rate, satiety threshold, and half-life of different DAT inhibitors in rats. The duration of lever-pressing following termination of drug access was correlated with the t(1/2) estimates, suggesting a relationship between the time needed for animals to stop lever pressing and the PK properties of the agonist.
Article
Chemistry, Multidisciplinary
Jonathan D. Dabbs, Megan N. Ericson, Justin H. Wilde, Rachel F. Lombardo, Earl C. Ashcraft, Diane A. Dickie, W. Dean Harman
Summary: The efficacy of methylphenidate (MPH) as a dopamine receptor agonist makes it a potential therapeutic for cocaine addiction. In this study, scientists explored the functionalization of the piperidine ring, which has not been previously investigated for MPH derivatives. Through a series of reactions, functional groups were successfully added to the C5' position of the piperidyl ring, resulting in a library of potential drug candidates. The structures of these compounds were confirmed through comprehensive analysis.
ACS CENTRAL SCIENCE
(2023)
Article
Medicine, Research & Experimental
Phillip M. Mackie, Adithya Gopinath, Dominic M. Montas, Alyssa Nielsen, Aidan Smith, Rachel A. Nolan, Kaitlyn Runner, Stephanie M. Matt, John McNamee, Joshua E. Riklan, Kengo Adachi, Andria Doty, Adolfo Ramirez-Zamora, Long Yan, Peter J. Gaskill, Wolfgang J. Streit, Michael S. Okun, Habibeh Khoshbouei
Summary: Monocyte-derived macrophages play crucial roles in tissue homeostasis and diseases, regulated by various signaling molecules. Recent studies have shown the ability of biogenic amines to control macrophage functions, with a focus on the mechanisms surrounding immune cells remaining unclear. Investigating the functions of norepinephrine transporter (NET) and dopamine transporter (DAT) on human MDMs, researchers found that DAT may play a potential role in regulating innate immunity through an immunomodulatory mechanism mediated by LPS-induced dopamine reverse transport.
Review
Neurosciences
Melinda Hersey, Amanda K. Bacon, Lydia G. Bailey, Mark A. Coggiano, Amy H. Newman, Lorenzo Leggio, Gianluigi Tanda
Summary: The rapid increase in individuals affected by psychostimulant use disorder (PSUD) has highlighted the potential of Modafinil (MOD) as a therapeutic option due to its non-addictive properties, despite its similar mechanism of action to commonly abused psychostimulants on the dopamine transporter (DAT). Clinical and preclinical studies have demonstrated the efficacy of MOD in treating symptoms related to PSUD and other psychiatric disorders involving alterations of brain dopamine systems.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Pengju Yan, Ningning Li, Ming Ma, Zhaoli Liu, Huicui Yang, Jinnan Li, Chunlei Wan, Shuliu Gao, Shuai Li, Longtai Zheng, John L. Waddington, Lin Xu, Xuechu Zhen
Summary: This study reveals that roxadustat upregulates HIF-1α expression, resulting in cellular iron deficiency and functional accumulation of dopamine transporter (DAT), which inhibits conditioned place preference (CPP) induced by morphine or methamphetamine (METH).
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
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)