Article
Biochemistry & Molecular Biology
Soichiro Ide, Noriaki Iwase, Kenichi Arai, Masahiro Kojima, Shigeru Ushiyama, Kaori Taniko, Kazutaka Ikeda
Summary: Despite the widespread use of opioids for pain management, opioid addiction and the overdose crisis are becoming increasingly serious. A new nonpeptide ligand, UD-030, has been found to be a selective mu-opioid receptor antagonist and shows promise as a treatment option for opioid use disorder, with different characteristics from traditional medications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Substance Abuse
Tapio Paljarvi, John Strang, Patrick D. Quinn, Sierra Luciano, Seena Fazel
Summary: The study aimed to establish and quantify the association between abuse-deterrent formulation (ADF) oxycodone and 1-year risk of opioid-related harm. After analyzing electronic medical records of more than 70 million patients, researchers found that patients with a new prescription of abuse-deterrent formulation oxycodone may be at an increased risk of opioid-related harm.
Article
Behavioral Sciences
S. Mogali, P. Askalsky, G. Madera, J. D. Jones, S. D. Comer
Summary: Minocycline may enhance the analgesic effects of opioids by attenuating their abuse liability.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2021)
Article
Pharmacology & Pharmacy
Beth Youngblood, Kevin Li, Donald R. Gehlert, Julio C. Medina, Neil Schwartz
Summary: Opioid use disorder (OUD) is a significant socioeconomic burden, and an ideal pharmacotherapy should balance benefits and risks to alleviate the suffering associated with opioid withdrawal and cravings while inhibiting abuse.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Anna Dari, Stefan Buller, Michael Gautrois, Hans-Juergen Stahlberg, Jens Rengelshausen, Jan Freijer
Summary: This study utilized an integrated approach to understand the effects of oxycodone pharmacokinetics on mu-opioid receptor binding and employed a two-step modeling approach to analyze the data. The results showed that the PK of oxycodone can be described by a two-compartmental model, and the new data confirmed the PK/PD model established using prior information, providing estimates for key parameters.
CLINICAL PHARMACOKINETICS
(2021)
Article
Medicine, General & Internal
Jonathan S. Zipursky, Karl Everett, Tara Gomes, J. Michael Paterson, Ping Li, Peter C. Austin, Muhammad Mamdani, Joel G. Ray, David N. Juurlink
Summary: This study examined the risk of using codeine and oxycodone for postpartum pain relief, and found that the use of oxycodone was not associated with an increased risk of persistent opioid use, except after vaginal delivery.
CANADIAN MEDICAL ASSOCIATION JOURNAL
(2023)
Article
Neurosciences
Kim Juhani Blomqvist, Katarzyna Anna Dudek, Hanna Viisanen, Kert Matlik, Fredrik Harry Gustav Ahlstrom, Jouko Laitila, Eija Anneli Kalso, Pekka Veli Rauhala, Tuomas Olavi Lilius
Summary: Opioids are effective in managing severe pain, however, tolerance and adverse effects limit their use. The role of peripheral opioid receptors in analgesia and tolerance is still unclear. This study suggests that peripherally restricted opioid receptor antagonist, methylnaltrexone, may not prevent morphine tolerance and morphine tolerance is mediated by central opioid receptors in rats.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Neurosciences
Megan J. Moerke, S. Stevens Negus
Summary: The study aimed to examine the time parameters of enhanced opioid reward after initial opioid exposure. Results showed that the enhanced opioid reward was relatively transient, but could be produced by a range of different dosing frequencies.
PSYCHOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Ariana C. Brice-Tutt, Darrice S. Montgomery, Cassidy M. Kramer, Peter M. Novotny, Wendi L. Malphurs, Abhisheak Sharma, Robert. M. Caudle, Adriaan W. Bruijnzeel, Barry Setlow, John K. Neubert, Niall P. Murphy
Summary: This study found that there are inter-relationships between pain sensitivity, drug reward, and drug misuse. Rats were tested for pain sensitivity, conditioned place preference to oxycodone, and the impact of neuropathic pain on pain sensitivity and reinstatement of conditioned place preference. The results suggest that high rates of behavioral sensitization predict faster rates of extinction of oxycodone seeking/reward, and cutaneous thermal reflex pain may be predictive of both.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Yan Yan, Bridget Truitt, Junyi Tao, Sean Michael Boyles, Danielle Antoine, William Hulme, Sabita Roy
Summary: The cycle of substance use disorder leading to dependence is a complex process involving multiple neurocircuitries and brain regions. This study focused on the amygdala, a core brain region involved in withdrawal, anxiety, and depressive-like behaviors, to examine the transcriptional changes in different cell types during substance use disorder. Using single-cell RNA sequencing, the researchers classified all cell types in the mouse amygdala and identified distinct gene expression changes in glial cells during dependence compared to naive or withdrawal state. The findings provide unique insights into the biological processes involved in substance use disorder and the alterations in the brain.
Article
Biology
Iris Bachmutsky, Xin Paul Wei, Adelae Durand, Kevin Yackle
Summary: Opioids are highly effective analgesics but can lead to respiratory depression and death when used excessively. The development of biased agonists that provide pain relief without affecting breathing has been a focus of research. However, a study examining beta-arrestin 2-deficient mice found no link between beta-arrestin 2 and opioid respiratory depression, suggesting that the mechanism behind biased agonists' attenuated effect on breathing remains unclear.
Article
Pharmacology & Pharmacy
Edna J. Santos, Matthew L. Banks, S. Stevens Negus
Summary: The degree of mu opioid receptor (MOR) efficacy required to produce hyperactivity in mice was evaluated in this study. The results showed that the hyperactivity induced by MOR agonists is efficacy dependent and requires relatively high levels of MOR agonist efficacy for its full expression.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Jacob A. Beierle, Emily J. Yao, Stanley I. Goldstein, William B. Lynch, Julia L. Scotellaro, Anyaa A. Shah, Katherine D. Sena, Alyssa L. Wong, Colton L. Linnertz, Olga Averin, David E. Moody, Christopher A. Reilly, Gary Peltz, Andrew Emili, Martin T. Ferris, Camron D. Bryant
Summary: Understanding the pharmacogenomics of opioid metabolism and behavior is crucial for successful treatment, as mutations can have significant effects on therapeutic efficacy and addiction vulnerability. This study reveals robust, sex-dependent differences in oxycodone behaviors and metabolite concentrations between BALB/c substrains. The findings suggest the involvement of candidate genes, particularly Zhx2, in regulating oxycodone metabolism in the brain.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Phil Skolnick
Summary: Overdose deaths and nonfatal opioid overdose have become major concerns in the opioid epidemic in the United States. The misuse of synthetic opioids, such as fentanyl and benzimidazoles, has contributed to the dramatic increase in overdose cases. Developing more effective reversal agents is crucial in combating opioid misuse.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Chemistry, Medicinal
Hongsong Feng, Rui Wang, Chang-Guo Zhan, Guo-Wei Wei
Summary: In this study, a deep generative model combining a stochastic differential equation (SDE)-based diffusion model with a pretrained autoencoder is proposed. The model efficiently generates molecules targeting multiple opioid receptors and evaluates their ADMET properties. Molecular optimization is performed to enhance the pharmacokinetic properties of lead compounds. Advanced binding affinity predictors are built using molecular fingerprints, providing a valuable tool for evaluating the pharmacological effects of the generated molecules.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)