ArticleJournal of medicinal chemistry2015
Structure-Activity Relationships of (+)-Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05685225 (Safety and Efficacy of Naltrexone/Acetaminophen for the Acute Treatment of Migraine), which is not on this map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety and Efficacy of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Single-Site, Phase 2 Randomized Trial
Who cites it
35 citing papers in PubMed, 95 citations in OpenAlex.
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- Naltrexone blocks alcohol-induced effects on kappa-opioid receptors in the plasma membrane.Translational psychiatry · 2024Article
- EnantioselectiveChemical communications (Cambridge, England) · 2024Article
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
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- New insights into the role of Klotho in inflammation and fibrosis: molecular and cellular mechanisms.Frontiers in immunology · 2024Review
- Low-dose naltrexone use for the management of post-acute sequelae of COVID-19.International immunopharmacology · 2023Article
- Recent Advances in Studying Toll-like Receptors with the Use of Computational Methods.Journal of chemical information and modeling · 2023Review
- Insight into TLR4 receptor inhibitory activityRSC advances · 2023Article
- Therapeutic trials for long COVID-19: A call to action from the interventions taskforce of the RECOVER initiative.Frontiers in immunology · 2023Review
- Angiotensin II receptor type 1 blocker candesartan improves morphine tolerance by reducing morphine‑induced inflammatory response and cellular activation of BV2 cells via the PPARγ/AMPK signaling pathway.Molecular medicine reports · 2022Article
- Neuropathic ocular surface pain: Emerging drug targets and therapeutic implications.Expert opinion on therapeutic targets · 2022Review
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- Immunometabolic Modulatory Role of Naltrexone in BV-2 Microglia Cells.International journal of molecular sciences · 2021Article
- Nicotine and its metabolite cotinine target MD2 and inhibit TLR4 signaling.Innovation (Cambridge (Mass.)) · 2021Article
- Toll-like receptor 2 and 4 antagonism for the treatment of experimental autoimmune encephalomyelitis (EAE)-related pain.Brain, behavior, and immunity · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of Toll-like receptors has been linked to neuropathic pain and opioid dependence. (+)-Naltrexone acts as a Toll-like receptor 4 (TLR4) antagonist and has been shown to reverse neuropathic pain in rat studies. We designed and synthesized compounds based on (+)-naltrexone and (+)-noroxymorphone and evaluated their TLR4 antagonist activities by their effects on inhibiting lipopolysaccharide (LPS) induced TLR4 downstream nitric oxide (NO) production in microglia BV-2 cells. Alteration of the N-substituent in (+)-noroxymorphone gave us a potent TLR4 antagonist. The most promising analog, (+)-N-phenethylnoroxymorphone ((4S,4aR,7aS,12bR)-4a,9-dihydroxy-3-phenethyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one, 1j) showed ∼75 times better TLR-4 antagonist activity than (+)-naltrexone, and the ratio of its cell viability IC50, a measure of its toxicity, to TLR-4 antagonist activity (140 μM/1.4 μM) was among the best of the new analogs. This compound (1j) was active in vivo; it significantly increased and prolonged morphine analgesia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.