Article
Chemistry, Multidisciplinary
Haoqing Wang, Florian Hetzer, Weijiao Huang, Qianhui Qu, Justin Meyerowitz, Jonas Kaindl, Harald Huebner, Georgios Skiniotis, Brian K. Kobilka, Peter Gmeiner
Summary: This study reported the structure of the mu-opioid receptor agonist PZM21 bound to mu OR in complex with G(i) protein, and its derivative FH210 with extremely low efficacy for arrestin recruitment. The study revealed a potential mechanism to reduce beta-arrestin recruitment by mu OR, holding promise for developing next-generation analgesics with fewer adverse effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Pharmacology & Pharmacy
Eamonn Kelly, Alexandra Conibear, Graeme Henderson
Summary: In ligand bias, different agonist drugs activate distinct signaling pathways, leading to different therapeutic and adverse effects. While it was believed that selectively activating the G protein-dependent pathway of the mu-opioid receptor would result in effective analgesia without adverse effects, recent data suggest that most effects are mediated by this pathway and some drugs described as biased may actually be low-intrinsic-efficacy agonists. This review discusses the current understanding of bias at the mu-opioid receptor and other opioid receptor subtypes.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Article
Neurosciences
C. Austin Zamarripa, Sally L. Huskinson, E. Andrew Townsend, Thomas E. Prisinzano, Bruce E. Blough, James K. Rowlett, Kevin B. Freeman
Summary: This study aimed to determine if the biased KOR agonists nalfurafine and triazole 1.1 could effectively reduce rhesus monkeys' choice for oxycodone. The results demonstrate that triazole 1.1 represents an important prototypical compound for developing novel KOR agonists as deterrents for prescription opioid abuse.
PSYCHOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Edward L. Stahl, Cullen L. Schmid, Agnes Acevedo-Canabal, Cai Read, Travis W. Grim, Nicole M. Kennedy, Thomas D. Bannister, Laura M. Bohn
Summary: G protein-biased mu opioid receptor agonists demonstrate stability in a wash-resistant signaling state and reversibility by antagonists. These biased agonists stimulate G protein signaling in mouse brains without competing with full agonist activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
C. Austin Zamarripa, Tanya Pareek, Hayley M. Schrock, Thomas E. Prisinzano, Bruce E. Blough, Kenneth J. Sufka, Kevin B. Freeman
Summary: Triazole 1.1 is a novel KOR agonist that can reduce the reinforcing effects of oxycodone and enhance oxycodone-induced antinociception to a degree similar to typical KOR agonists. Developing MOR-KOR agonist combinations from the triazole 1.1 series may lead to new pain therapeutics with reduced abuse liability.
PSYCHOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Xiang Li, Yanhao Guo, Jing Li, Zixing Yu, Jingchao Cheng, Fengxia Ren, Hongxin Jia, Yatong Zhang, Shiqiang Cui, Tao Zhang, Weiguo Shi
Summary: This study reports the design, synthesis, and evaluation of two classes of compounds as biased mu-opioid receptor agonists. Among them, SWG-LX-33 exhibits potent mu-opioid receptor agonist activity and analgesic effect, without activating the beta-arrestin signaling pathway.
Article
Behavioral Sciences
Rachel D. Altshuler, Kristine T. Garcia, Xuan Li
Summary: The study revealed that adolescents may show resistance to oxycodone relapse during early abstinence, but this resistance disappears quickly during the transition from adolescence to young adulthood. Group-housing plays a protective role against incubated oxycodone craving.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Jolien De Neve, Thomas M. A. Barlow, Dirk Tourwe, Frederic Bihel, Frederic Simonin, Steven Ballet
Summary: One of the main challenges in contemporary medicinal chemistry is the development of safer analgesics that can circumvent the severe side effects of the gold standard opioids. The discovery of biased agonism has exponentially increased the importance of this field in pharmacology over the past decade. New therapeutic molecules inducing biased response at opioid receptors show great promise in avoiding specific side effects.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Jacques D. Nguyen, Yanabel Grant, Michael A. Taffe
Summary: This study investigated the affective consequences of escalating prescription opioid use using rat models. The results showed that changes in brain reward function during escalated oxycodone self-administration are driven by an interplay between kappa-opioid receptor-mediated negative affective state associated with escalated oxycodone intake and dynamic restoration of brain reward status during longer periods of abstinence.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Richard A. Slivicki, Tom Earnest, Yu-Hsuan Chang, Rajesh Pareta, Eric Casey, Jun-Nan Li, Jessica Tooley, Kavitha Abiraman, Yvan M. Vachez, Drew K. Wolf, Jason T. Sackey, Dhinesh Kumar Pitchai, Terrill Moore, Robert W. Gereau Iv, Bryan A. Copits, Alexxai Kravitz, Meaghan C. Creed
Summary: The use of prescription opioids, particularly oxycodone, is a major driving force behind the current opioid epidemic. Designing a model to study oxycodone abuse presents various challenges, including the different pharmacokinetics and dynamics compared to other opioids like morphine or fentanyl. Factors such as intake pattern and the self-administration environment also play a crucial role in drug intake levels, behavioral sensitization, and propensity to relapse. To address these challenges, researchers have developed an oral, homecage-based oxycodone self-administration paradigm in mice, which demonstrates behavioral and physiological features relevant to prescription opioid abuse.
Article
Biochemistry & Molecular Biology
Maria Mavrikaki, Tania Lintz, Nick Constantino, Sarah Page, Elena Chartoff
Summary: Long-term use of opioid painkillers can lead to physical and psychological symptoms, with women more likely to use them for self-medication, but preclinical studies in both sexes are still lacking.
Article
Behavioral Sciences
Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich
Summary: In this study, researchers found that the effects and rewarding properties of oxycodone are not influenced by sex, but vary across the estrous cycle in female rats. These findings are important for the treatment and prevention of oxycodone misuse.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2023)
Review
Pharmacology & Pharmacy
Lucja Kudla, Ryszard Przewlocki
Summary: The development of G protein-biased opioid agonists shows promise in reducing opioid side effects, but data regarding their addictive properties are inconsistent. More research is needed to determine the potential of these compounds in addressing opioid addiction.
PHARMACOLOGICAL REPORTS
(2021)
Article
Chemistry, Medicinal
Jae-Hoon Jung, In Hee Jang, Yeo Ok Kim, Sunhong Kim, Myung Ha Yoon, Yong-Chul Kim
Summary: In this study, a selective Gi-biased mu-opioid receptor agonist was developed through design, synthesis and structure-activity relationship analysis. The agonist exhibited dose-dependent pain relief efficacy in in vivo experiments.
DRUG DEVELOPMENT RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Alena Randakova, Jan Jakubik
Summary: Cholinergic signalling disruption through muscarinic receptors is linked to various pathologies, with potential therapeutic benefits found in selective muscarinic agonists. The identical orthosteric binding site across all muscarinic receptor subtypes makes the development of affinity-based selective agonists nearly impossible. Functionally selective and biased agonists show promise for selectively targeting individual muscarinic receptor subtypes.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Obstetrics & Gynecology
William J. Lawson, Kristin Shirey, Redin A. Spann, Carlos A. Zamarripa, Jonathan P. Hosler, Bernadette E. Grayson
MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
(2017)
Article
Neurosciences
E. Andrew Townsend, Jennifer E. Naylor, S. Stevens Negus, Shelley R. Edwards, Hina N. Qureshi, Hunter W. McLendon, Christopher R. McCurdy, Coco N. Kapanda, Jussara M. do Carmo, Fernanda S. da Silva, John E. Hall, Kenneth J. Sufka, Kevin B. Freeman
PSYCHOPHARMACOLOGY
(2017)
Article
Neurosciences
C. Austin Zamarripa, Jennifer E. Naylor, Sally L. Huskinson, E. Andrew Townsend, Thomas E. Prisinzano, Kevin B. Freeman
PSYCHOPHARMACOLOGY
(2020)
Article
Behavioral Sciences
C. Austin Zamarripa, Tilak R. Patel, B. Cole Williams, Tanya Pareek, Hayley M. Schrock, Thomas E. Prisinzano, Kevin B. Freeman
BEHAVIOURAL PHARMACOLOGY
(2020)
Article
Clinical Neurology
Christiano dos Santos e Santos, Bradley A. Welch, Shelley R. Edwards, Kwamie K. Harris, Brittany C. Duncan, Alexandra R. Himel, Bernadette E. Grayson
Summary: This study used a rat model to investigate the impact of spinal cord injury on molecular and circulating, metabolic and immune biomarkers. The gene expression in the spinal cord was found to be associated with locomotor score, body weight, composition, and metabolic parameters. However, circulating levels of these proteins did not vary by injury or predict the level of locomotor recovery. This suggests the challenge of identifying stable markers of disease progression.
GLOBAL SPINE JOURNAL
(2022)
Article
Psychology, Biological
C. Austin Zamarripa, William S. Doyle, Kevin B. Freeman, James K. Rowlett, Sally L. Huskinson
Summary: This study evaluates the choice between cocaine and food under fixed and variable schedules, finding that the uncertainty in obtaining cocaine may lead to a greater preference for drug reinforcers over non-drug alternatives. Male monkeys tend to choose food associated with variable schedules, while both female and male monkeys tend to choose cocaine associated with variable schedules.
EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
(2023)
Article
Chemistry, Analytical
Dennis J. Sholler, C. Austin Zamarripa, Tory R. Spindle, Erin L. Martin, David Kuntz, Ryan Vandrey, Megan Grabenauer
Summary: Traditionally, smoking has been the main method for using cannabis, but now there are more alternative routes of administration. The focus of current research is on Delta(9)-THC-COOH as the main analyte. This study aims to characterize the urinary excretion profiles of Delta(9)-THC-COOH and other analytes following oral and vaporized cannabis administration, and to evaluate the sensitivity and specificity of different drug testing methods.
JOURNAL OF ANALYTICAL TOXICOLOGY
(2022)
Article
Substance Abuse
Catherine F. Moore, C. Austin Zamarripa, Elise M. Weerts
Summary: This study investigated the effects of acute and chronic treatment with pure CBD on alcohol seeking and consumption behaviors in male baboons. The results showed that CBD did not significantly reduce alcohol seeking, self-administration, or intake. Drinking patterns were also not altered. Therefore, pure CBD is not an effective pharmacotherapy for reducing excessive drinking.
DRUG AND ALCOHOL DEPENDENCE
(2023)
Article
Surgery
Katherine C. Benedict, Somjade J. Songcharoen, Kristin L. Stephens, Anna L. Winter, Shelley R. Edwards, Christopher A. Campbell, Peter B. Arnold
Summary: This study evaluated the impact of different methods on postoperative complications following chemoradiotherapy and abdominoplevic tumor resection. The results showed no significant difference in postoperative complications between VRAM (vertical rectus abdominis myocutaneous flap) and BIGAP/IGAP (bilateral/inferior gluteal artery perforator fasciocutaneous flap) closure techniques. Therefore, flap reconstruction is a viable choice for these challenging defects.
JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY
(2023)
Article
Medicine, Research & Experimental
Redin A. Spann, William J. Lawson, Gene L. Bidwell, C. Austin Zamarripa, Rodrigo O. Maranon, Sibali Bandyopadhyay, Erin R. Taylor, Jane F. Reckelhoff, Michael R. Garrett, Bernadette E. Grayson