Nanodaru · OPRK1 · Small Molecule
naltrexone is a small molecule developed by Nanodaru. It is approved for therapeutic indications via injectable (others) or intramuscular (im) injection.
| Brand Names | Exopio |
| Company | Nanodaru |
| Drug Class | Small Molecule |
| Molecular Target | OPRK1, OPRM1 |
| Route | Injectable (Others), Intramuscular (IM) Injection |
| Status | Approved |
naltrexone acts on 2 molecular targets:
| OPRK1 | opioid receptor kappa 1 (KOR1, OPRK) |
| OPRM1 | opioid receptor mu 1 (MOR1, LMOR) |
naltrexone is developed for 2 unique indications across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Psychiatric disorders | Alcoholism | ✓ Approved |
| Psychiatric disorders | Drug dependence | ✓ Approved |
Liang Chen-Wei CW, Lee Yao-Tung YT, Wang Jiunn-Kae JK
Shen Mary R MR, Owusu-Boaitey Kwadwo K, Murphy Zackari D ZD, Rains Alex N AN et al.
Opioid use disorder (OUD) remains a major public health crisis despite evidence-based medications, including methadone, buprenorphine, and naltrexone. Persistent challenges with treatment retention, access, stigma, and incomplete response highlight the need for adjunctive pharmacotherapies targeting neurobiological systems beyond the mu-opioid receptor. We conducted a narrative review of emerging pharmacologic approaches for OUD and opioid withdrawal syndrome, focusing on ketamine and NMDA receptor antagonists, cannabinoids, psychedelics, and incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists. Ketamine has preliminary randomized evidence suggesting potential effects on abstinence, withdrawal, craving, and psychotherapy augmentation. Cannabidiol may reduce cue-induced craving and anxiety, whereas dronabinol may modestly suppress opioid withdrawal symptoms. Psychedelic research, particularly involving ibogaine, shows observational signals for withdrawal reduction and abstinence but is limited by safety concerns, regulatory barriers, and sparse controlled evidence. Incretin-based therapies have generated strong observational signals linking GLP-1-based treatment to reduced overdose and OUD-related outcomes, though prospective trials remain limited. Across these therapeutic classes, convergent mechanisms include modulation of mesolimbic reward circuitry, cue-reactivity, stress responsivity, neuroplasticity, and cognitive flexibility. Future studies should prioritize rigorous blinding assessment, active comparators, objective endpoints, standardized cue-reactivity measures, diverse samples, and careful safety monitoring. Regulatory policies should facilitate the development and implementation of future research in novel therapies for OUD.
Grant Stephen N SN, Mulcahy Matthew J MJ, Lester Henry A HA
Opioid receptor antagonists increase the plasma membrane density of μ-opioid receptors (MOR) in vivo, thereby inducing "supersensitivity" to opioid agonists. This phenomenon increases the risk of overdose in patients that were being treated with naltrexone (Ntx), a popular MOR antagonist. Although there are many studies on the effects of ligands on the plasma membrane density of MORs, their effects on MOR trafficking from the endoplasmic reticulum (ER) via endoplasmic reticulum exit sites (ERES) have not been investigated. Using fluorescently tagged Sec24 to visualize ERES and a highly ER-retained μ-opioid receptor (MOR) point mutant, MOR[N190K], we measured ERES levels after incubation in various opioid receptor ligands. Data from sensitized emission Förster resonance energy transfer (FRET) show that MOR[N190K] interacts with Sec24D. We observe that Ntx, naloxone, morphine, and fentanyl increase the fraction of the cytoplasm occupied by ERES. In contrast, buprenorphine, methadone, and two allosteric modulators have no substantial effect on ERES levels. Mutating S375, an important phosphorylation site for MOR internalization, decreased morphine and fentanyl's pharmacological chaperoning abilities but did not affect Ntx's pharmacological chaperoning abilities. Ntx did not change intracellular cyclic adenosine monophosphate (cAMP) concentrations, so global trafficking is not expected to change. We also find that antagonist-induced pharmacological chaperoning depends on retrotransport from the Golgi as brefeldin A (BFA) treatment prevented pharmacological chaperoning. These data reveal new understandings of how opioid ligands change MOR trafficking from the ER and can help us better understand the pathophysiology of opioid use disorder.
Satcher Milan F MF, Saunders Elizabeth C EC, Bell Kathleen D KD, Moore Sarah K SK et al.
Individuals with opioid use disorder (OUD) who return to the community from incarceration face a high risk of fatal drug overdose. This mortality risk is related to significant barriers to accessing health care, social support, and resources needed to transition to and thrive within the community safely. Digital health tools have effectively supported substance use treatment and recovery, but their potential to support OUD during the high-risk period of reentry is underexplored. This study aimed to examine how adults with OUD returning from incarceration perceive and engage with digital health tools, and identify barriers and facilitators to their use. Semistructured interviews were conducted with a purposive sample of 39 adults recently released from New Hampshire prisons and jails. Participants were recruited from a randomized clinical trial (EXIT-CJS) comparing the effectiveness of extended-release buprenorphine, naltrexone, and enhanced treatment as usual on treatment retention. Interviews were audio recorded, transcribed, and analyzed using a deductive-inductive approach to content analysis. The COREQ (Consolidated Criteria for Reporting Qualitative Research) criteria were used to guide the study reporting. Most participants preferred digital health over in-person care for both OUD treatment and other health care, mainly due to its convenience and resilience against reentry challenges. Yet, most participants also underscored the irreplaceable role of in-person therapeutic human connection in recovery and recognized this as a trade-off of stand-alone digital health. Participants described using digital health tools to overcome barriers that otherwise would have prevented them from receiving in-person care, such as transportation shortages, limited provider availability, and work scheduling conflicts. Accessing digital health was acknowledged as contingent on access to internet-capable devices, affordable connectivity, and digital literacy. The findings suggest that maximizing digital health's impact in reentry will require a multipronged approach: investing in infrastructure to close the digital divide, addressing upstream structural barriers to accessing care, and partnering with impacted persons to co-design hybrid care models that enhance the feasibility of engaging in care during reentry while enhancing therapeutic human connection and respecting patient preferences.
Allen Victoria V, Cook Jocelynn L JL, Chandrasekaran Nirmala N, Christie Janet J et al.
To establish national standards of care for screening and counselling pregnant women and individuals of reproductive age regarding alcohol consumption and alcohol use disorder. Health care providers who care for pregnant women and women of childbearing age. Pregnant women and women of childbearing age and their families. Medline, EMBASE, and CENTRAL databases were searched for "alcohol use and pregnancy". The results were filtered for a publication date between October 2018 and February 2026. The search terms were developed using the MeSH terms and key words including: pre-pregnancy, pregnant, breast feeding, lactation, female, women, preconception care, prenatal care, Fetal Alcohol Spectrum Disorder, prenatal alcohol exposure, drinking behavior, alcohol abstinence, alcohol drinking, binge drinking, Alcohol-Related Disorders, alcoholism, alcohol consumption, alcohol abuse, benzodiazepines, disulfiram, naltrexone, acamprosate, ondansetron, topiramate, cyanamide, calcium carbimide, alcohol deterrents, disease management, detoxification, Alcoholics Anonymous, alcohol counselling, harm reduction, pre-pregnancy care, prenatal care, incidence, prevalence, epidemiological monitoring, brief intervention. Clinical trials, observational studies, reviews, systematic reviews and meta-analysis, guidelines, and conference consensus were included. The table of evidence from the search that supports the recommendations is included as Appendix B. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and conditional recommendations). Implementation of the recommendations in these guidelines may increase obstetrical care provider recognition of alcohol consumption and problematic alcohol use among women of childbearing age or who are pregnant using validated screening tools and brief intervention approaches. Obstetrician-gynecologists should be given priority access to healthcare professionals with expertise in alcohol cessation for their patients in order to support optimal health and pregnancy outcomes. As they are already responsible for the urgent management of pregnancy-related complications, they must be able to rely on expedited referral pathways to ensure timely interventions. RECOMMENDATIONS: (Recommendations IN BOLD are new to this guideline update; an overview of the updated supporting literature for all recommendations is provided in Appendix B).
Comer Sandra D SD, Mondello Jamie E JE, Castillo Felipe F
To understand the use of naltrexone for the treatment of Opioid Use Disorder (OUD). We reviewed different formulations' effectiveness, clinical hurdles, potential safety concerns, and explored how specific sub-populations fared on naltrexone. The review followed PRISMA-ScR guidelines and was registered in Open Science Framework (hs3g6). We included searches of the MEDLINE, Embase, and Cochrane Central Databases, using predetermined eligibility criteria, including English language studies from 1984 to 2026 investigating naltrexone treatment for OUD. Extracted data included: publication year, country, study type, naltrexone formulation, treatment setting, comparator, key findings, and limitations. Our search yielded 3219 references and 181 were ultimately included. Most studies were randomized controlled studies and secondary analyses (58%), involved injectable formulations (61.3%), and were conducted in the United States (57.5%). We identified patient characteristics and settings associated with better outcomes, including inpatient setting, highly motivated patients, and patients with prescription opioid use history, among others. Naltrexone induction remains a clinical hurdle and treatment cessation carries risk of subsequent overdose. Naltrexone is the least utilized medication for OUD because of induction-related clinical hurdles despite its comparable post-stabilization effectiveness with other medications for OUD. Further research is warranted on how to expand its clinical use.
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