Review
Gastroenterology & Hepatology
Karim Chamie, Vishnukamal Golla, Andrew T. Lenis, Patrick M. Lec, Siamak Rahman, Eugene R. Viscusi
Summary: PAMORAs, as peripherally acting mu-opioid receptor antagonists, have the potential to alleviate postoperative ileus and opioid-induced constipation by blocking peripheral effects of opioids in the gastrointestinal tract while maintaining their analgesic properties in the central nervous system. Further research is needed to explore the therapeutic potential of PAMORAs in the management of POI and postoperative OIC.
JOURNAL OF GASTROINTESTINAL SURGERY
(2021)
Article
Biochemistry & Molecular Biology
Kristina Puls, Helmut Schmidhammer, Gerhard Wolber, Mariana Spetea
Summary: This study comprehensively evaluated the binding and activity of the peripheral opioid analgesic HS-731 at all opioid receptors using in silico methods. The results provide insights into the interaction patterns of HS-731 with the opioid receptors, highlighting the importance of specific amino acid residues for recognition and partial agonism. Additionally, experimental evidence showed the absence of affinity of HS-731 to the NOP receptor, with a specific amino acid residue preventing binding to the orthosteric binding pocket.
Review
Medicine, General & Internal
Martina Rekatsina, Antonella Paladini, Asbjorn M. Drewes, Farrah Ayob, Omar Viswanath, Ivan Urits, Oscar Corli, Joseph Pergolizzi, Giustino Varrassi
Summary: Opioids are commonly used for treating chronic and acute pain, but can lead to adverse events such as opioid-induced bowel dysfunction, specifically opioid-induced constipation. Peripherally acting mu-opioid receptor antagonists (PAMORAs) have been developed to counteract these effects. Different PAMORAs have varying efficacy and tolerability profiles, with naloxegol and naldemedine showing promising results in reducing opioid-induced constipation.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Pediatrics
Chris Novak, Amanda Hogg, Kyle Sue, Dawn Davies
Summary: This study evaluated the efficacy and safety of methylnaltrexone and naloxegol in hospitalized children, including those with critical illness. The median time to the first bowel movement after the first dose of PAMORA was 15.5 hours, with 63% of patients experiencing laxation within 24 hours of the first dose. No significant adverse events were observed. Future studies should include larger samples of patients with critical illness and postoperative OIC.
PAEDIATRICS & CHILD HEALTH
(2021)
Article
Oncology
Antoine Lemaire, Yoann Pointreau, Berengere Narciso, Francois-Xavier Piloquet, Viorica Braniste, Jean-Marc Sabate
Summary: This study demonstrates that naloxegol is effective and well-tolerated in cancer pain patients with OIC, leading to an improvement in their quality of life.
SUPPORTIVE CARE IN CANCER
(2021)
Review
Oncology
Ana Fernandez-Montes, Guillermo de Velasco, Santiago Aguin, Cristina Farriols, Maria Guirado-Risueno, Vanessa G. Jerviz-Guia, Maria Victoria Baeza-Nadal, Rodolfo Chicas-Sett, Jose Luis Firvida, Francisco Garcia-Navalon, Patricia Martin, Carmen Perezagua-Marin, Dulce Rodriguez, Joan Santamaria, Tamara Sauri, Manuel Cobo
Summary: The management of chronic pain is crucial for improving the quality of life for cancer and palliative care patients, but long-term use of opioid-based treatments can lead to constipation as a major adverse effect. Peripherally acting mu-opioid receptor antagonists (PAMORAs) have emerged as new effective drugs for managing opioid-induced constipation (OIC), however, there is limited information available on their use in real-life practice for cancer patients.
CURRENT TREATMENT OPTIONS IN ONCOLOGY
(2021)
Article
Pediatrics
Ethan L. L. Gillett, Clint A. A. Layes, Lee Crawley, Stephen M. M. Schexnayder
Summary: Naloxegol is effective in increasing stool output in critically ill children receiving opioids without an increase in withdrawal symptoms.
CLINICAL PEDIATRICS
(2023)
Article
Multidisciplinary Sciences
Md Tariqul Haque Tuhin, Dengpan Liang, Fang Liu, Hala Aldawod, Toufiq Ul Amin, Joshua S. Ho, Rasha Emara, Arjun D. Patel, Melanie A. Felmlee, Miki S. Park, James A. Uchizono, Mamoun M. Alhamadsheh
Summary: The study develops a drug delivery approach to limit the passage of small molecules across the blood-brain barrier, and also develops new potent analgesics that have a significant impact on the central nervous system.
NATURE COMMUNICATIONS
(2022)
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
Health Care Sciences & Services
Montserrat Olmo, Jesus Gonzalez-Barboteo, Deborah Moreno, Eva Coma, Gala Serrano
Summary: This case report describes a cancer patient who developed acute opioid withdrawal symptoms due to the interaction between the opioid antagonist naloxone and naloxegol. Switching to oxycodone/naloxone led to severe adverse reactions, which were only controlled after intravenous morphine administration. Recommendations include avoiding the combination of naloxone and naloxegol or using it with extreme caution and tolerance monitoring.
BMJ SUPPORTIVE & PALLIATIVE CARE
(2021)
Article
Pediatrics
Chris Novak, Amanda Hogg, Kyle Sue, Dawn Davies
Summary: This study evaluated the effectiveness and safety of methylnaltrexone and naloxegol in treating constipation in hospitalized children. Results showed that nearly two-thirds of patients experienced laxation within 24 hours of the first dose, with no significant adverse events observed. Future studies should focus on larger patient populations, including those with critical illness and postoperative constipation.
PAEDIATRICS & CHILD HEALTH
(2021)
Review
Biochemistry & Molecular Biology
Zoe Li, Jie Liu, Fan Dong, Nancy Chang, Ruili Huang, Menghang Xia, Tucker A. Patterson, Huixiao Hong
Summary: The United States is facing a severe opioid crisis, with increasing numbers of deaths caused by both prescription and illegal opioids over the past two decades. Opioids are important for pain treatment but also highly addictive, making it difficult to combat this public health issue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Mathias E. Cook, Cecilie S. Knoph, Camilla A. Fjelsted, Jens B. Frokjaer, Anders E. Bilgrau, Srdan Novovic, Maiken Thyregod Jorgensen, Michael B. Mortensen, Liv B. J. Nielsen, Amer Hadi, Mark Berner-Hansen, Wiktor Rutkowski, Miroslav Vujasinovic, Matthias Lohr, Asbjorn M. Drewes, Soren S. Olesen
Summary: This study aims to investigate whether naldemedine can alter the natural course of pancreatitis in patients with recurrent acute pancreatitis and improve patient outcomes.
Review
Pharmacology & Pharmacy
Stuart M. Brierley, Luke Grundy, Joel Castro, Andrea M. Harrington, Gerhard Hannig, Michael Camilleri
Summary: This article discusses the mechanisms and effects of GC-C agonists, such as linaclotide, in the treatment of irritable bowel syndrome (IBS).
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Kana Yasufuku, Katsumi Koike, Mika Kobayashi, Hiroki Chiba, Motoji Kitaura, Shino Takenouchi, Minoru Hasegawa, Yasuhide Morioka, Hirokazu Mishima, Tsutomu Suzuki, Masahide Fujita
Summary: The study suggests that peripheral MOR is involved in tramadol-induced constipation, with naldemedine being able to block the inhibitory effect of tramadol on small intestinal transit.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2021)