ArticleBrain research2015
In vitro and in vivo efficacy of a potent opioid receptor agonist, biphalin, compared to subtype-selective opioid receptor agonists for stroke treatment.
Article in Brain research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The neuropeptide in ischemic brain injury: insights, challenges, and horizon of targeted interventions.Journal of translational medicine · 2026Pooled it
- Permeability of Metformin across an In Vitro Blood-Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs).Pharmaceutics · 2023Article
- Targeting organic cation transporters at the blood-brain barrier to treat ischemic stroke in rats.Experimental neurology · 2022Article
- Short-term exposure to JUUL electronic cigarettes can worsen ischemic stroke outcome.Fluids and barriers of the CNS · 2022Article
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 2022Review
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Biphalin-A Potent Opioid Agonist-As a Panacea for Opioid System-Dependent Pathophysiological Diseases?International journal of molecular sciences · 2021Review
- Naltrexone is neuroprotective against traumatic brain injury in mu opioid receptor knockout mice.CNS neuroscience & therapeutics · 2021Article
- The role of peptidase neurolysin in neuroprotection and neural repair after stroke.Neural regeneration research · 2021Article
- Peptidase neurolysin functions to preserve the brain after ischemic stroke in male mice.Journal of neurochemistry · 2020Article
- Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists.Biomolecules · 2020Article
- Brain Delivery of a Potent Opioid Receptor Agonist, Biphalin during Ischemic Stroke: Role of Organic Anion Transporting Polypeptide (OATP).Pharmaceutics · 2019Article
- Neurovascular unit transport responses to ischemia and common coexisting conditions: smoking and diabetes.American journal of physiology. Cell physiology · 2019Review
- Modulation of Opioid Transport at the Blood-Brain Barrier by Altered ATP-Binding Cassette (ABC) Transporter Expression and Activity.Pharmaceutics · 2018Review
- The non-peptidic δ-opioid receptor agonist Tan-67 mediates neuroprotection post-ischemically and is associated with altered amyloid precursor protein expression, maturation and processing in mice.Journal of neurochemistry · 2018Article
- Blood-Brain Barrier Protection as a Therapeutic Strategy for Acute Ischemic Stroke.The AAPS journal · 2017Review
- Peptides at the blood brain barrier: Knowing me knowing you.Peptides · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
To meet the challenge of identification of new treatments for stroke, this study was designed to evaluate a potent, nonselective opioid receptor (OR) agonist, biphalin, in comparison to subtype selective OR agonists, as a potential neuroprotective drug candidate using in vitro and in vivo models of ischemic stroke. Our in vitro approach included mouse primary neuronal cells that were challenged with glutamate and hypoxic/aglycemic (H/A) conditions. We observed that 10nM biphalin, exerted a statistically significant neuroprotective effect after glutamate challenge, compared to all selective opioid agonists, according to lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, 10nM biphalin provided superior neuroprotection after H/A-reoxygenation compared to selective opioid agonists in all cases. Our in vitro investigations were supported by in vivo studies which indicate that the nonselective opioid agonist, biphalin, achieves enhanced neuroprotective potency compared to any of the selective opioid agonists, evidenced by reduced edema and infarct ratios. Reduction of edema and infarction was accompanied by neurological improvement of the animals in two independent behavioral tests. Collectively these data strongly suggest that concurrent agonist stimulation of mu, kappa and delta ORs with biphalin is neuroprotective and superior to neuroprotection by activation of any single OR subtype.
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What OpenQuestion holds
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.