Article
Neurosciences
Julia E. R. Nickols, Serdar M. Dursun, Anna M. W. Taylor
Summary: Opioid addiction is characterized by changes in the dopamine system, and the use of dopamine partial agonists like brexpiprazole may help restore dopamine signaling during drug withdrawal. In a mouse model, brexpiprazole treatment was found to attenuate locomotor sensitization, abolish morphine place preference, and prevent the expression of opioid-induced hyperalgesia.
Article
Endocrinology & Metabolism
Jing Xia, Bin Wang, Shuai Han, Xuequan Liu, Haichen Chu, Yanlin Bi
Summary: This study observed the effect of berberine on morphine-induced acute constipation in mice. The results showed that berberine did not change defecation function, but it completely reversed morphine-induced activation of PI3K/Akt/NF-kB signaling pathway, thus ameliorating colonic inflammation.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Oncology
Siyin Wu, Tian Jin, Bingjie Ma, Yun Ji, Xuehua Huang, Peiliang Wang, Xiaoming Liu, Boris V. Krylov, Xianguo Liu, Ke Ma
Summary: The effects of oral administration of magnesium-L-threonate on the analgesic effect of opioids in patients with advanced cancer were investigated in this study. The results showed that compared to the placebo group, the L-TAMS group had improved analgesic effect and reduced opioid dosage, as well as significant relief of opioid-induced constipation.
Article
Neurosciences
Dillon J. McGovern, Abigail M. Polter, Emily D. Prevost, Annie Ly, Connor J. McNulty, Bodhi Rubinstein, David H. Root
Summary: A three-neuron model of VTA opioid function has been discovered, involving a mu-opioid receptor gated VTA glutamate neuron pathway to VTA dopamine neurons. These glutamate-Mu opioid receptor neurons are distributed in the anterior VTA, while the majority of VTA mu-opioid receptor neurons are GABAergic neurons in the posterior VTA. Optogenetic stimulation of VTA glutamate neurons can induce excitatory currents in VTA dopamine neurons, regulated by the mu-opioid receptor.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Substance Abuse
John J. Mariani, Robert L. Dobbins, Amy Heath, Frank Gray, Howard Hassman
Summary: This study shows that rapid induction of extended-release buprenorphine treatment is feasible and well-tolerated for patients with opioid use disorder, regardless of their fentanyl use status. The results suggest comparable patient retention and clinical response following single-day induction of BUP-XR for patients who are fentanyl-positive and fentanyl-negative.
AMERICAN JOURNAL ON ADDICTIONS
(2023)
Article
Pharmacology & Pharmacy
Agnieszka Karbownik, Danuta Szkutnik-Fiedler, Tomasz Grabowski, Anna Wolc, Joanna Stanislawiak-Rudowicz, Radoslaw Jazwiec, Edmund Grzeskowiak, Edyta Szalek
Summary: This study evaluated the potential pharmacokinetic drug-drug interactions between sorafenib and morphine, finding that morphine significantly increased plasma concentrations of sorafenib and its active metabolite, while sorafenib significantly increased the exposure to morphine and its metabolite, indicating potential clinical significance in cancer therapy with both improved response and increased risk of adverse effects.
Article
Multidisciplinary Sciences
Yeona Kang, Kelly A. O'Conor, Andrew C. Kelleher, Joseph Ramsey, Abolghasem Bakhoda, Seth M. Eisenberg, Wenjing Zhao, Tyler Stodden, Torben D. Pearson, Min Guo, Nina Brown, Jeih-San Liow, Joanna S. Fowler, Sung Won Kim, Nora D. Volkow
Summary: The rise in opioid overdoses in the US is driven by potent synthetic opioids like fentanyl. Naloxone can effectively reverse overdoses from conventional opioids, but higher doses may be needed for fentanyls. PET scans showed that clinically relevant doses of naloxone can displace fentanyls in the brain, but the duration of naloxone's occupancy at opioid receptors is short-lived.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Alberto Bracci, Matthieu Nadini, Maxwell Aliapoulios, Damon McCoy, Ian Gray, Alexander Teytelboym, Angela Gallo, Andrea Baronchelli
Summary: The study reveals that dark web marketplaces (DWMs) quickly offered COVID-19 related products in response to the pandemic, but decreased their supply as the regular economy met the demand. The impact of the pandemic on DWMs' overall activity, especially recreational drugs, is significant.
Review
Biochemistry & Molecular Biology
Ali Alipour Najmi, Rainer Bischoff, Hjalmar P. Permentier
Summary: N-dealkylation is an important chemical transformation for the synthesis of pharmaceuticals and chemicals, as well as a crucial metabolic pathway in vivo. The identification and synthesis of drug metabolites has significant implications in drug development studies.
Article
Clinical Neurology
Yaqi Bian, Xiufen Wang, Jian-Hui Liang, Lin Li, Xue Wu, Benqin Tang, George Pak-Heng Leung, Simon Ming-Yuen Lee
Summary: A study developed a morphine-induced behavioral sensitization model in adult zebrafish, finding that withdrawal time significantly affects behavioral sensitization and may involve dopaminergic, glutamatergic, and opioid systems.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Psychiatry
Xiangning Xue, Wei Zong, Jill R. Glausier, Sam-Moon Kim, Micah A. Shelton, BaDoi N. Phan, Chaitanya Srinivasan, Andreas R. Pfenning, George C. Tseng, David A. Lewis, Marianne L. Seney, Ryan W. Logan
Summary: Severe disruptions to sleep and circadian rhythms are common in individuals with opioid use disorder (OUD). This study investigates molecular rhythm changes in the brains of individuals with OUD compared to unaffected subjects. The results suggest that transcriptional rhythms in key brain areas involved in OUD are disrupted, and these disruptions are associated with altered neurotransmission and sleep-related traits in opioid addiction.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Computer Science, Artificial Intelligence
Chuanbo Hu, Minglei Yin, Bin Liu, Xin Li, Yanfang Ye
Summary: Illicit drug trafficking on social media platforms like Instagram has become a serious issue, making it difficult to identify drug dealers from the data. Existing methods focus on posting, while this research establishes a large-scale multimodal dataset for identifying drug dealers.
ACM TRANSACTIONS ON INTELLIGENT SYSTEMS AND TECHNOLOGY
(2021)
Article
Medicine, Legal
Julio de Carvalho Ponce, Luiz Ferreira Neves Neves Junior, Ana Carolina Stosch da Silva, Luiz Carlos Liberatori, Priscila Vieira de Medeiros
Summary: This case report discusses an uncommon drug seizure case where cocaine was found in herbs that are typically used to deliver synthetic cannabinoids, rather than the usual powder or crack form. The report also includes a comparison of the physical appearance and chemical results of genuine coca leaves.
FORENSIC SCIENCE INTERNATIONAL
(2022)
Article
Pharmacology & Pharmacy
Ali Ahmadian Salami, Mohaddeseh Sadat Alavi, Mohammad Saeid Souri, Ali Roohbakhsh
Summary: This study evaluated the pharmacological effects of TRPA1 inhibition on morphine. The results showed that the TRPA1 antagonist HC030031 reduced morphine-induced conditioned place preference and physical dependence.
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
(2022)
Article
Microbiology
Andreas Hintz, Tim Umland, Gero Niess, Mehtap Guendogdu, Anika Moerner, Frank Tacke
Summary: The study compared the co-medication profiles of PWID, OST, and patients undergoing HCV therapy, finding that most patients had co-medication with nervous system drugs being the most commonly prescribed. While potential DDIs with HCV therapies were relatively low, caution should be taken during treatment.
Review
Chemistry, Medicinal
Joshua W. Conner, Daniel P. Poole, Manuela Jorg, Nicholas A. Veldhuis
Summary: This review addresses the key challenges, synthesis approaches, and structure-activity relationships in recent fluorescent small molecule studies for GPCRs, and discusses the advantages of using high-resolution GPCR structures to inform conjugation strategies.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Lena Gottesman-Katz, Rocco Latorre, Stephen Vanner, Brian L. Schmidt, Nigel W. Bunnett
Summary: Chronic pain is a complex issue with mechanisms that are not fully understood and current treatments being inadequate. Recent studies on G protein-coupled receptors have shed light on potential new approaches for chronic pain management, offering insights into both the structure and function of these receptors. By targeting specific GPCRs and utilizing biased agonists or allosteric modulators, there is promise for developing more effective and targeted therapies for chronic pain in the future.
Editorial Material
Physiology
Sue C. Bodine, Heddwen L. Brooks, Nigel W. Bunnett, Hilary A. Coller, Mark R. Frey, Bina Joe, Thomas R. Kleyman, Merry L. Lindsey, Andre Marette, Rory E. Morty, Jan-Marino Ramirez, Morten B. Thomsen, Gina L. C. Yosten
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2021)
Article
Oncology
Francesco De Logu, Matilde Marini, Lorenzo Landini, Daniel Souza Monteiro de Araujo, Niccolo Bartalucci, Gabriela Trevisan, Gennaro Bruno, Martina Marangoni, Brian Lee Schmidt, Nigel W. Bunnett, Pierangelo Geppetti, Romina Nassini
Summary: Depleting sciatic nerve resident macrophages in mice alleviated mechanical/cold hypersensitivity and spontaneous pain caused by melanoma or lung carcinoma cells. This was mediated by upregulation of M-CSF, expansion of resident macrophages, TRPA1 activation, and oxidative stress. Depletion of macrophages in a portion of the nerve prevented pain-like behaviors, indicating a pathway involving M-CSF, macrophages, oxidative stress, and Schwann cell TRPA1 in cancer pain.
Article
Gastroenterology & Hepatology
Nestor Nivardo Jimenez-Vargas, Yang Yu, Dane D. Jensen, Diana Daeun Bok, Matthew Wisdom, Rocco Latorre, Cintya Lopez, Josue O. Jaramillo-Polanco, Claudius Degro, Mabel Guzman-Rodriguez, Quentin Tsang, Zachary Snow, Brian L. Schmidt, David E. Reed, Alan Edward Lomax, Kara Gross Margolis, Christoph Stein, Nigel W. Bunnett, Stephen J. Vanner
Summary: The fentanyl analogue NFEPP demonstrated effectiveness in inhibiting pain response in mice with colitis in an acidic environment, without causing respiratory depression, constipation, or hyperactivity. In contrast, fentanyl inhibited pain responses in both groups of mice and had side effects such as respiratory depression and hyperactivity.
Article
Medicine, Research & Experimental
Jeffri S. Retamal, Megan S. Grace, Larissa K. Dill, Paulina Ramirez-Garcia, Scott Peng, Arisbel B. Gondin, Felix Bennetts, Sadia Alvi, Pradeep Rajasekhar, Juhura G. Almazi, Simona E. Carbone, Nigel W. Bunnett, Thomas P. Davis, Nicholas A. Veldhuis, Daniel P. Poole, Peter McIntyre
Summary: Serotonin (5-HT) mediates tissue edema and inflammation via the 5-HT2A receptor, TRPV4 activation, and neuropeptide release. Endothelial and epithelial cells act as physical barriers modulating fluid and molecule exchange, influenced by GPCR and ion channel signaling.
LABORATORY INVESTIGATION
(2021)
Article
Gastroenterology & Hepatology
Jesse J. DiCello, Simona E. Carbone, Ayame Saito, Vi Pham, Agata Szymaszkiewicz, Arisbel B. Gondin, Sadia Alvi, Kiliana Marique, Priyank Shenoy, Nicholas A. Veldhuis, Jakub Fichna, Meritxell Canals, Arthur Christopoulos, Celine Valant, Daniel P. Poole
Summary: This study investigates the modulation of delta opioid receptor in the enteric nervous system using allosteric modulators, demonstrating the potential of positive allosteric modulation as a pharmacological approach to enhance opioid receptor signaling and suppress colonic motility. The findings suggest that allosteric modulation of opioid receptor signaling could be a therapeutic strategy for conditions such as irritable bowel syndrome.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Gastroenterology & Hepatology
Stephen J. Keely, Andreacarola Urso, Alexandr Ilyaskin, Christoph Korbmacher, Nigel W. Bunnett, Daniel P. Poole, Simona E. Carbone
Summary: Bile acids play important regulatory roles in intestinal motility and electrolyte transport. Advances in studying their receptors, transporters, and ion channels have provided new insights into the molecular mechanisms involved in these processes. Recognizing bile acids and their modulated ion channels as potential targets could lead to new approaches for treating gastrointestinal disorders.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Neurosciences
Scott Peng, Daniel P. Poole, Nicholas A. Veldhuis
Summary: TRPV4 is a polymodal cation channel that plays a key role in various physiological processes, and its activation may be associated with inflammation and pain. Research has shown that TRPV4 can be regulated by a variety of endogenous stimuli.
NEUROSCIENCE LETTERS
(2022)
Article
Multidisciplinary Sciences
Rocco Latorre, Alan Hegron, Chloe J. Peach, Shavonne Teng, Raquel Tonello, Jeffri S. Retamal, Rafael Klein-Cloud, Diana Bok, Dane D. Jensen, Lena Gottesman-Katz, Jeanette Rientjes, Nicholas A. Veldhuis, Daniel P. Poole, Brian L. Schmidt, Charalabos H. Pothoulakis, Carl Rankin, Ying Xie, Hon Wai Koon, Nigel W. Bunnett
Summary: This study investigated the localization and signaling of protease-activated receptor 2 (PAR(2)) in colitis, revealing that PAR(2) endocytosis sustains protease-evoked inflammation and nociception. PAR(2) in endosomes is a potential therapeutic target for colitis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Thanh-Nhan Nguyen, Ghizal Siddiqui, Nicholas A. Veldhuis, Daniel P. Poole
Summary: Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel that regulates macrophage activity and phenotype, influencing immune response and inflammatory diseases. While TRPV4 is generally considered pro-inflammatory, it may also have anti-inflammatory effects. However, the detailed mechanisms of TRPV4 in inflammatory diseases are still limited.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Rocco Latorre, Paulina D. Ramirez-Garcia, Alan Hegron, James L. Grace, Jeffri S. Retamal, Priyank Shenoy, Mai Tran, Luigi Aurelio, Bernard Flynn, Daniel P. Poole, Rafael Klein-Cloud, Dane D. Jensen, Thomas P. Davis, Brian L. Schmidt, John F. Quinn, Michael R. Whittaker, Nicholas A. Veldhuis, Nigel W. Bunnett
Summary: Stable star polymer nanostars that release antagonists continuously for 24 hours provide effective and long-lasting relief from chronic pain by disrupting endosomal signaling.
Review
Physiology
Chloe J. Peach, Laura E. Edgington-Mitchell, Nigel W. Bunnett, Brian L. Schmidt
Summary: Proteases are signaling molecules that control cellular functions through cleaving protease-activated receptors (PARs). Understanding the structure and function of PARs has led to the development of drug antagonists, offering potential for the treatment of major diseases.
PHYSIOLOGICAL REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Ayame Saito, Sadia Alvi, Celine Valant, Arthur Christopoulos, Simona E. Carbone, Daniel P. Poole
Summary: The enteric nervous system plays a crucial role in regulating gastrointestinal motility. Disrupted enteric nervous system activity can lead to dysmotility. Pharmacological treatment options for dysmotility involve targeting G protein-coupled receptors (GPCRs) expressed by enteric nervous system neurons. Current drugs that target GPCRs for motility disorders have drawbacks such as significant side-effects and a loss of physiological tone. Allosteric modulation of GPCRs, which bind to a distinct site from the endogenous ligand, may provide effective relief from motility disorders while minimizing side-effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Alan Hegron, Chloe J. Peach, Raquel Tonello, Philipp Seemann, Shavonne Teng, Rocco Latorre, Harald Huebner, Dorothee Weikert, Jeanette Rientjes, Nicholas A. Veldhuis, Daniel P. Poole, Dane D. Jensen, Alex R. B. Thomsen, Brian L. Schmidt, Wendy L. Imlach, Peter Gmeiner, Nigel W. Bunnett
Summary: The hypothesis that sustained GPCR signaling from endosomes mediates pain is supported by the finding that specific GPCR antagonists can inhibit endosomal signals and relieve pain. The role of natural GPCR variants in pain maintenance is also explored. It is discovered that substance P can induce the assembly of endosomal signaling complexes, and that sustained inhibition of endosomal signals leads to long-lasting antinociceptive effects. These findings provide insight into the potential treatment strategies for diverse diseases involving GPCR signaling in intracellular locations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)