Review
Biochemistry & Molecular Biology
Shan Liu, Wen-Jia Kang, Anna Abrimian, Jin Xu, Luca Cartegni, Susruta Majumdar, Patrick Hesketh, Alex Bekker, Ying-Xian Pan
Summary: The OPRM1 gene undergoes extensive alternative splicing to produce multiple splice variants with important pharmacological implications for the actions of opioid drugs. These variants can mediate distinct effects of various mu opioids and be targeted for the development of novel analgesics with potent efficacy against multiple types of pain while reducing side effects associated with traditional opiates.
Article
Oncology
Hao Zhang, Mengdi Qu, Aysegul Gorur, Zhirong Sun, Juan P. Cata, Wankun Chen, Changhong Miao
Summary: This study focused on the relationship between opioid use and MOR expression in patients with stage I-III PDAC. The results showed that MOR is not an independent predictor of poor survival in this stage of PDAC but is associated with perineural invasion. Patients requiring high amounts of opioids intraoperatively have worse outcomes if they express high levels of MOR.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wenjian Kang, Shan Liu, Jin Xu, Anna Abrimian, Ayma F. Malik, Raymond Chien, Adejuyigbe Adaralegbe, Akwasi Amponsah, Luca Cartegni, John Pintar, Ying-Xian Pan
Summary: The mu opioid receptor gene OPRM1 undergoes extensive alternative pre-mRNA splicing to generate multiple splice variants, which have distinct pharmacological functions. Gene-targeted mouse models have been used to study the functional importance of these splice variants in the actions of mu opioids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elsa Cortes-Montero, Maria Rodriguez-Munoz, M. Carmen Ruiz-Cantero, Enrique J. Cobos, Pilar Sanchez-Blazquez, Javier Garzon-Nino
Summary: TRPA1 channels are involved in nociceptive signaling, forming functional associations with MORs and NMDARs to promote pain transmission and modulate analgesic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Jennifer M. Bossert, Carlos A. Mejias-Aponte, Thomas Saunders, Lindsay Altidor, Michael Emery, Ida Fredriksson, Ashley Batista, Sarah M. Claypool, Kiera E. Caldwell, David J. Reiner, Jonathan J. Chow, Matthew Foltz, Vivek Kumar, Audrey Seasholtz, Elizabeth Hughes, Wanda Filipiak, Brandon K. Harvey, Christopher T. Richie, Francois Vautier, Juan L. Gomez, Michael Michaelides, Brigitte L. Kieffer, Stanley J. Watson, Huda Akil, Yavin Shaham
Summary: By introducing the Oprm1-Cre knock-in transgenic rat, this study investigated the role of the mu-opioid receptor (MOR) in heroin self-administration. The study found that heroin self-administration showed different patterns in male and female Oprm1-Cre rats. This research provides new strategies for understanding the involvement of MOR-expressing cells in opioid addiction, pain-related behaviors, and other opioid-mediated functions.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Alba Vidal-Torres, Begona Fernandez-Pastor, Monica Garcia, Eva Ayet, Anna Cabot, Javier Burgueno, Xavier Monroy, Bertrand Aubel, Xavier Codony, Luz Romero, Rosalia Pascual, Maria Teresa Serafini, Gregorio Encina, Carmen Almansa, Daniel Zamanillo, Manuel Merlos, Jose Miguel Vela
Summary: WLB-73502 is a dual compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. It exhibits analgesic efficacy with a better safety profile compared to strong opioids.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Cell Biology
Aysegul Gorur, Miguel Patino, Ted Shi, German Corrales, Hideaki Takahashi, Roberto Rangel, Frederico O. Gleber-Netto, Curtis Pickering, Jeffrey N. Myers, Juan P. Cata
Summary: The study suggests that the expression and activity of Mu-opioid receptor (MOR) play a key role in the proliferation, invasion, and migration of head and neck squamous cell carcinoma (HNSCC) cells, and the antagonist methylnaltrexone (MNTX) shows inhibitory effects on HNSCC cell lines.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Laura Agullo, Isidro Aguado, Javier Muriel, Cesar Margarit, Alba Gomez, Monica Escorial, Astrid Sanchez, Alicia Fernandez, Ana M. Peiro
Summary: Variability in analgesic response due to genetic polymorphisms can be reduced through genotype-guided opioid prescribing. This study found that genotype-guided treatment led to improved pain relief, increased quality of life, and reduced adverse events and opioid dose in chronic pain patients. The findings suggest that implementing genotype-guided treatment could have positive clinical and economic outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Javier Cuitavi, Lucia Hipolito, Meritxell Canals
Summary: Opioid receptors are crucial targets for pain treatment, but targeting them therapeutically brings significant challenges and has led to the current opioid crisis due to misuse of opioid drugs.
TRENDS IN BIOCHEMICAL SCIENCES
(2021)
Article
Neurosciences
Taylor G. Brown, Jin Xu, Yasmin L. Hurd, Ying-Xian Pan
Summary: This study investigates the potential role of OPRM1 splice variants in heroin addiction. The results show similar expression patterns of OPRM1 splice variants in humans and rats, but dysregulated expression of certain splice variants in heroin abusers. These findings suggest that OPRM1 splice variants may play an important role in heroin addiction.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Neurosciences
Volker Neugebauer, Peyton Presto, Vadim Yakhnitsa, Nico Antenucci, Brianna Mendoza, Guangchen Ji
Summary: Neuroplasticity in cortico-limbic circuits is important in pain persistence and modulation. The amygdala plays a key role in the emotional dimension of pain, and interactions with prefrontal cortical regions change in pain conditions. Other regions in the limbic system are also involved in pain modulation. The corticolimbic system contains opioids and opioid receptors, and their modulatory effects and potential opposing functions are still not fully understood.
Article
Biochemistry & Molecular Biology
Hongguang Ma, Mengchu Li, Piyusha P. Pagare, Huiqun Wang, Nima Nassehi, Edna J. Santos, S. Stevens Negus, Dana E. Selley, Yan Zhang
Summary: This study synthesized a series of bivalent ligands to investigate the functional interactions between opioid and chemokine receptors. Compound 1a showed promising antinociceptive effect and may serve as a novel chemical probe for developing more potent bivalent ligands for chronic pain management.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Ramajayam Kuppusamy, Ying-Ting Hsu, Yi-Yu Ke, Po-Wei Chang, Yung-Chiao Chang, Hsiao-Fu Chang, Pei-Chen Wang, Yu-Hao Lin, Yu-Chen Huang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Chuan Shih, Chiung-Tong Chen, Shiu-Hwa Yeh, Shau-Hua Ueng
Summary: This study modified the structure of a previously identified compound and discovered a new, potent analgesic with reduced side effects. The analgesic activated mu-opioid receptors through specific signaling pathways and showed weak effects on other related receptors. It exhibited strong antinociception in pain and allodynia models with less gastrointestinal inhibition and tolerance compared to morphine.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Nathan Gaddis, Ravi Mathur, Jesse Marks, Linran Zhou, Bryan Quach, Alex Waldrop, Orna Levran, Arpana Agrawal, Matthew Randesi, Miriam Adelson, Paul W. Jeffries, Nicholas G. Martin, Louisa Degenhardt, Grant W. Montgomery, Leah Wetherill, Dongbing Lai, Kathleen Bucholz, Tatiana Foroud, Bernice Porjesz, Valgerdur Runarsdottir, Thorarinn Tyrfingsson, Gudmundur Einarsson, Daniel F. Gudbjartsson, Bradley Todd Webb, Richard C. Crist, Henry R. Kranzler, Richard Sherva, Hang Zhou, Gary Hulse, Dieter Wildenauer, Erin Kelty, John Attia, Elizabeth G. Holliday, Mark McEvoy, Rodney J. Scott, Sibylle G. Schwab, Brion S. Maher, Richard Gruza, Mary Jeanne Kreek, Elliot C. Nelson, Thorgeir Thorgeirsson, Kari Stefansson, Wade H. Berrettini, Joel Gelernter, Howard J. Edenberg, Laura Bierut, Dana B. Hancock, Eric Otto Johnson
Summary: In this study, genomic structural equation modeling was used to conduct a genome-wide association study of opioid addiction (OA) phenotypes. Significant associations were found between OA and the genes OPRM1, PPP6C, and FURIN, suggesting pleiotropy in addiction and related traits.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Giuliana Costanzo, Rita Turnaturi, Carmela Parenti, Salvatore Spoto, Silvia Piana, Maria Dichiara, Chiara Zagni, Anna Rita Galambos, Nariman Essmat, Agostino Marrazzo, Emanuele Amata, Mahmoud Al-Khrasani, Lorella Pasquinucci
Summary: In this study, we investigated the pharmacological properties of LP1 analogs both in vitro and in vivo to develop compounds with improved analgesic effects. By modifying the structure of the N-substituent of LP1, we found that compounds 3 and 7 displayed high binding affinity for the mu opioid receptor (MOR) and showed antagonist or agonist effects in different assays. Compound 7, as potent as LP1 and DAMGO, demonstrated analgesic effects in thermal and inflammatory pain models.
Correction
Neurosciences
Masayo Fujita, Yukiko Ochiai, Taishi-Clark Takeda, Yoko Hagino, Kazuto Kobayashi, Kazutaka Ikeda
Article
Health Care Sciences & Services
Soichiro Ide, Miharu Nakanishi, Syudo Yamasaki, Kazutaka Ikeda, Shuntaro Ando, Mariko Hiraiwa-Hasegawa, Kiyoto Kasai, Atsushi Nishida
Summary: This study investigated the association between loot box purchasing among adolescents and parents, and problem online gaming. The results showed that adolescent loot box purchasing is linked to problem online gaming, but not with parents' loot box purchasing. Measures to reduce these behaviors should target reducing addictive symptoms in young video gamers.
JMIR SERIOUS GAMES
(2021)
Article
Biochemistry & Molecular Biology
Yukiko Ochiai, Masayo Fujita, Yoko Hagino, Kazuto Kobayashi, Ryoichi Okiyama, Kazushi Takahashi, Kazutaka Ikeda
Summary: Some diseases associated with dopamine deficiency, like Parkinson's disease, are accompanied by psychiatric symptoms. However, the mechanism behind this is not clear. Previous studies have shown that dopamine-deficient mice display hyperactivity in new environments, which can be improved by certain medications. In this study, the researchers aimed to identify the pharmacological mechanism of psychiatric symptoms associated with dopamine deficiency in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Daisuke Nishizawa, Takeshi Terui, Kunihiko Ishitani, Shinya Kasai, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Kazutaka Ikeda
Summary: Considerable individual differences in sensitivity to opioids have been observed. In a genome-wide association study of cancer pain patients, specific SNPs were found to be significantly associated with opioid analgesic requirements. These findings may contribute to personalized pain treatment.
Review
Biochemistry & Molecular Biology
Hiroko Kotajima-Murakami, Soichiro Ide, Kazutaka Ikeda
Summary: Substance use disorders (SUDs) are chronic disorders with serious consequences that alter brain function. GIRK channels play a key role in the effects of addictive substances, and GIRK channel modulators like Ifenprodil may be potential medications for addiction treatment.
Article
Neurosciences
Masayo Fujita, Yukiko Ochiai, Yoko Hagino, Kazuto Kobayashi, Geoffrey Pavey, Brian Dean, Kazutaka Ikeda
Summary: Dopamine-deficient (DD) mice show hyperactivity, which may be related to a decrease in muscarinic signaling. The study found a decrease in the density of muscarinic acetylcholine receptor M2 (CHRM2) in the cortex of DD mice. Additionally, both CHRM1/CHRM4 agonist xanomeline and CHRM2 agonist arecaidine propargyl ester tosylate inhibited hyperactivity in DD mice, suggesting the involvement of postsynaptic CHRM1 and CHRM2 and presynaptic CHRM2 in DD mice hyperactivity.
Article
Biochemistry & Molecular Biology
Daisuke Nishizawa, Tsutomu Mieda, Miki Tsujita, Hideyuki Nakagawa, Shigeki Yamaguchi, Shinya Kasai, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Akira Kitamura, Hirotomo Shimizu, Tadayuki Takashima, Masakazu Hayashida, Kazutaka Ikeda
Summary: The sensitivity to opioids varies among individuals. In this study, a three-stage genome-wide association study was conducted to identify potential genetic variations associated with the individual differences in the minimum effective concentration (MEC) of fentanyl in patients who underwent laparoscopic-assisted colectomy. The study revealed that a specific intergenic SNP (rs966775) was significantly associated with the plasma and effect-site MEC of fentanyl over specific postoperative periods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rikuhei Tsuchida, Daisuke Nishizawa, Ken-ichi Fukuda, Tatsuya Ichinohe, Kuniyuki Kano, Makoto Kurano, Kazutaka Ikeda, Masahiko Sumitani
Summary: A study on 362 healthy patients and 89 patients with cancer-related pain found that the ENPP2 gene polymorphisms rs7832704 and rs2249015 were significantly associated with opioid dose requirements, but not with postoperative pain intensity. This association was also validated in patients with cancer-related pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Chitra Vinnakota, Anna Schroeder, Xin Du, Kazutaka Ikeda, Soichiro Ide, Masayoshi Mishina, Matthew Hudson, Nigel Charles Jones, Suresh Sundram, Rachel Anne Hill
Summary: This study investigated the role of the GluN2D subunit in mediating schizophrenia-relevant behaviors induced by a range of NMDAR antagonists. The results showed that GluN2D-KO mice exhibited abnormal locomotor activity, anxiety-related behavior, and memory, and the effects of NMDAR antagonists were dependent on sex and genotype.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Article
Oncology
Daisuke Nishizawa, Ryozo Morino, Rie Inoue, Seii Ohka, Shinya Kasai, Junko Hasegawa, Yuko Ebata, Kyoko Nakayama, Hiroyuki Sumikura, Masakazu Hayashida, Miyuki Yokota, Kazutaka Ikeda
Summary: This study identified several genetic variations associated with the vulnerability to PONV through a genome-wide association study (GWAS), providing valuable information for predicting the vulnerability to PONV.
Article
Neurosciences
Naotaka Izuo, Hajime Miyanishi, Daisuke Nishizawa, Takuma Fujii, Junko Hasegawa, Naomi Sato, Fumihiko Tanioka, Haruhiko Sugimura, Kazutaka Ikeda, Atsumi Nitta
Summary: This study found no correlation between the DNA methylation status of the SHATI/NAT8L gene and smoking dependence, highlighting the need for identifying peripheral biomarkers to predict the effectiveness of smoking cessation therapy.
NEUROPSYCHOPHARMACOLOGY REPORTS
(2023)
Article
Neurosciences
Miho Tanaka, Atsushi Sato, Hiroko Kotajima-Murakami, Hirofumi Kashii, Yoko Hagino, Soichiro Ide, Kazutaka Ikeda
Summary: The study found that offspring of 3-month-old fathers exhibited social preference behavior, while offspring of 12- or 15-month-old fathers did not show similar behavior. Although the study was exploratory, it demonstrated an interaction between social behavior and paternal age in offspring of the same paternal mice.
NEUROPSYCHOPHARMACOLOGY REPORTS
(2022)
Article
Neurosciences
Moe Soeda, Seii Ohka, Daisuke Nishizawa, Junko Hasegawa, Kyoko Nakayama, Yuko Ebata, Ken-ichi Fukuda, Kazutaka Ikeda
Summary: Genetic polymorphisms of SLC17A9 and P2RY12 genes are associated with the development of phantom tooth pain, indicating a role of genes in PTP.
Review
Neurosciences
Atsushi Sato, Kazutaka Ikeda
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with the hyperactivation of mTORC1. Through studies on rodent models and clinical trials, mTORC1 inhibitors are considered promising therapeutics for treating ASD associated with mTORC1 activation.
BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE
(2022)
Review
Neurosciences
Masahiko Sumitani, Daisuke Nishizawa, Jun Hozumi, Kazutaka Ikeda
Summary: Opioid analgesics are the mainstay of cancer pain management, but there are barriers due to inadequate knowledge and risks of misuse and addiction. Genetic assessments could play an important role in overcoming these challenges.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)