Review
Biochemistry & Molecular Biology
Melinda Hersey, Mattingly K. Bartole, Claire S. Jones, Amy Hauck Newman, Gianluigi Tanda
Summary: Psychostimulant use disorders (PSUD) have significant public health and economic burdens, with sex differences observed in dependence onset, relapse rates, and treatment success. These differences may be related to neurochemical differences in the dopaminergic system, with females showing greater effects during the high estradiol phase. Women are more likely to start drug use at younger ages and exhibit higher desire for cocaine compared to men. Modafinil, a DAT inhibitor used for narcolepsy and sleep disorders, shows promise in treating PSUD, and its therapeutic potential is discussed in this review.
Article
Biochemistry & Molecular Biology
Melinda Hersey, Andy Y. Chen, Mattingly K. Bartole, Jayati Anand, Amy Hauck Newman, Gianluigi Tanda
Summary: Understanding the neurochemistry of sex differences in psychostimulant use disorders is crucial for developing effective therapies. This study utilized fast scan cyclic voltammetry to investigate dopamine dynamics in the nucleus accumbens shell of male and female mice. The findings suggest that cocaine has different effects on dopamine clearance and stimulation of the nucleus accumbens in male and female mice. Modafinil and its analogs show potential as therapeutic options for psychostimulant use disorders, with varying effects on dopamine dynamics.
ACS CHEMICAL NEUROSCIENCE
(2023)
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)
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)
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)
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
Shima Kouhnavardi, Alev Ecevitoglu, Vladimir Dragacevic, Fabrizio Sanna, Edgar Arias-Sandoval, Predrag Kalaba, Michael Kirchhofer, Jana Lubec, Marco Niello, Marion Holy, Martin Zehl, Matthias Pillwein, Judith Wackerlig, Rita Murau, Andrea Mohrmann, Kathryn R. Beard, Harald H. Sitte, Ernst Urban, Claudia Sagheddu, Marco Pistis, Roberto Plasenzotti, John D. Salamone, Thierry Langer, Gert Lubec, Francisco J. Monje
Summary: Dopamine and DAT signaling dysfunctions are associated with various neuropsychiatric disorders and progressive brain diseases, leading to devastating personal and familial concerns and high socioeconomic costs worldwide.
Article
Biochemistry & Molecular Biology
Iva Spreitzer, Josefin Keife, Tobias Strasser, Predrag Kalaba, Jana Lubec, Winfried Neuhaus, Gert Lubec, Thierry Langer, Judith Wackerlig, Irena Loryan
Summary: This study compared the tissue distribution and metabolism of S-CE-123 and R-modafinil, two dopamine transporter inhibitors, with a focus on their distribution in the central nervous system. The findings revealed distinct differences between the two compounds, with S-CE-123 demonstrating superior transport across the blood-brain barrier and blood-spinal cord barrier. In terms of cellular membrane transport, S-CE-123 primarily localized in the brain interstitial space, while R-modafinil distributed more evenly. Additionally, S-CE-123 showed significantly faster hepatic metabolism compared to R-modafinil. These findings suggest that S-CE-123 has potential as a candidate for the treatment of cognitive decline.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Nuria de Zavalia, Konrad Schoettner, Jory A. Goldsmith, Pavel Solis, Sarah Ferraro, Gabrielle Parent, Shimon Amir
Summary: The study reveals that the expression levels of Bmal1 and Per2 in the mouse striatum may have a gender-dependent impact on alcohol consumption propensity, with deletion of Bmal1 resulting in increased alcohol intake in males and decreased intake in females.
COMMUNICATIONS BIOLOGY
(2021)
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
Neurosciences
Sonia Aroni, Valeria Serra, Marco Bortolato, Roberto Frau, Miriam Melis
Summary: Vulnerability to cocaine use disorder is influenced by a combination of genetic and environmental factors. This study focuses on the interaction between allelic variants of the MAOA gene and early life stress (ES) in predisposition to cocaine abuse. The results demonstrate that the combination of low-activity alleles of the MAOA gene and ES increases sensitivity to cocaine's effects on dopamine neurons and impairs GABA synaptic efficacy. Additionally, the activation of dopamine D2 and CB1 receptors plays a role in the expression of these effects. The findings contribute to our understanding of the neural mechanisms underlying vulnerability to early onset cocaine use.
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.
Article
Pharmacology & Pharmacy
David S. Jacobs, Bruce E. Blough, Stephen J. Kohut
Summary: The study evaluated the abuse potential of methamphetamine's levorotatory isomer L-MA in nonhuman primates, finding that L-MA had significantly lower reinforcing effectiveness compared to other drugs. Chronic treatment with L-MA did not significantly alter daily activity and only temporarily suppressed food-reinforced responding.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Wei Xu, Xiaozhao Wang, Aaron M. Tocker, Peng Huang, Maarten E. A. Reith, Lee-Yuan Liu-Chen, Amos B. Smith, Sandhya Kortagere
ACS CHEMICAL NEUROSCIENCE
(2017)
Article
Chemistry, Medicinal
Sudharshan Madapa, Satishkumar Gadhiya, Thomas Kurtzman, Ian L. Alberts, Steven Ramsey, Maarten Reith, Wayne W. Harding
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Sathya Challasivakanaka, Juan Zhen, Margaret E. Smith, Maarten E. A. Reith, James D. Foster, Roxanne A. Vaughan
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Juan Zhen, Maarten E. A. Reith
JOURNAL OF NEUROCHEMISTRY
(2018)
Article
Chemistry, Medicinal
Maarten E. A. Reith, Kymry T. Jones, Juan Zhen, Sid Topiol
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2018)
Article
Pharmacology & Pharmacy
Sarah R. Mikelman, Bipasha Guptaroy, Kyle C. Schmitt, Kymry T. Jones, Juan Zhen, Maarten E. A. Reith, Margaret E. Gnegy
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2018)
Article
Biochemistry & Molecular Biology
Asma Elmabruk, Banibrata Das, Deepthi Yedlapudi, Liping Xu, Tamara Antonio, Maarten E. A. Reith, Aloke K. Dutta
ACS CHEMICAL NEUROSCIENCE
(2019)
Meeting Abstract
Neurosciences
Michael Lisieski, Arman Harutyunyan, Banibrata Das, Israel Liberzon, Frank Bymaster, Timothy Hsu, Maarten Reith, Shane. Perrine, Aloke Dutta
BIOLOGICAL PSYCHIATRY
(2019)
Article
Neurosciences
Courtney A. Marshall, Zachary D. Brodnik, Ole V. Mortensen, Maarten E. A. Reith, Jed S. Shurnsky, Barry D. Waterhouse, Rodrigo A. Espana, Sandhya Kortagere
Article
Pharmacology & Pharmacy
Wei Xu, Maarten E. A. Reith, Lee-Yuan Liu-Chen, Sandhya Kortagere
PHARMACOLOGICAL RESEARCH
(2019)
Article
Pharmacology & Pharmacy
Aloke K. Dutta, Soumava Santra, Arman Harutyunyan, Banibrata Das, Michael J. Lisieski, Liping Xu, Tamara Antonio, Maarten E. A. Reith, Shane A. Perrine
EUROPEAN JOURNAL OF PHARMACOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Kumaresan Jayaraman, Anand K. Das, Dino Luethi, Daniel Szoellosi, Gerhard J. Schuetz, Maarten E. A. Reith, Harald H. Sitte, Thomas Stockner
Summary: Transporters of the SLC6 family mediate neurotransmitter reuptake, forming various quaternary structures that support the activity of release-type psychostimulants. Single molecule microscopy experiments have revealed differences in stoichiometry between individual members.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Soumava Santra, Sandhya Kortagere, Seenuvasan Vedachalam, Sanjib Gogoi, Tamara Antonio, Maarten E. A. Reith, Aloke K. Dutta
Summary: The study revealed a significant influence from the alteration of the stereochemistry of the hydroxyl group on the pyran ring of D-473 on transporters affinities, indicating stereospecific preference for interaction. Furthermore, novel compounds such as D-528 and D-529 were identified as some of the most potent dopamine-norepinephrine reuptake inhibitors known to-date. Computational analysis found that the nature of interactions from molecular docking experiments correlated well with the affinities of the compounds for the transporters.
ACS CHEMICAL NEUROSCIENCE
(2021)
Meeting Abstract
Neurosciences
Frank Bymaster, Timothy Hsu, Michael Lisieski, Arman Harutyunyan, Banibrata Das, Israel Liberzon, Maarten Reith, Shane Perrine, Aloke Dutta
NEUROPSYCHOPHARMACOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy Stemmler, Maarten E. A. Reith, Aloke K. Dutta
ACS CHEMICAL NEUROSCIENCE
(2017)