ReviewFrontiers in neuroscience2022
Ceftriaxone as a Novel Therapeutic Agent for Hyperglutamatergic States: Bridging the Gap Between Preclinical Results and Clinical Translation.
Review in Frontiers in neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Effects of MC-100093, GLT-1 enhancer, in mesolimbic brain regions of C57BL/6 mouse exposed to hydrocodone high-dose challenge using comprehensive laboratory monitoring system.IBRO neuroscience reports · 2026Article
- Preventive Treatment With Ceftriaxone Attenuates Neuropathic Pain and Anxiety-Like Behaviour in a Mouse Model of Partial Sciatic Nerve Ligation.European journal of pain (London, England) · 2026Article
- The genetic architecture of epilepsy across molecular mechanisms and clinical heterogeneity.Epilepsia open · 2026Review
- Cerebroprotective potential of ceftriaxone against cadmium chloride-induced cerebral inflammatory changes and oxidative insult.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- MC-100093, a synthetic beta-lactam compound, and ceftriaxone modulate nicotine consumption, neuroinflammation and glutamatergic transporters in a nicotine self-administration mouse model.Psychopharmacology · 2026Article
- MC-350013 and Corylin Emerge as Promising Neuroprotective Agents through Dual Targeting of xCT and GLT-1.Journal of molecular neuroscience : MN · 2026Article
- A potential drug target in epilepsy and its role in other neurological disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Glial-Dopamine crosstalk: Astrocytic and microglial gatekeepers of neuroinflammation, plasticity, and motivation.AIMS neuroscience · 2026Review
- Neuroprotective effects of ceftriaxone after severe traumatic brain injury in male rats: a behavioral, biochemical, and histological study.Annals of medicine and surgery (2012) · 2026Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Neural Correlates of Huntington's Disease Based on Electroencephalography (EEG): A Mechanistic Review and Discussion of Excitation and Inhibition (E/I) Imbalance.Journal of clinical medicine · 2025Review
- Ceftriaxone affects ferroptosis and alleviates glial cell activation in Parkinson's disease.International journal of molecular medicine · 2025Article
- Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine.International journal of molecular sciences · 2025Review
- Neural correlates of β-lactam exposure in intensive care unit patients: an observational, prospective cohort study.Journal of neurology · 2025Observational
- Astrocytes in Rodent Anxiety-Related Behavior: Role of Calcium and Beyond.International journal of molecular sciences · 2025Review
- Metabolomic Profile Modification in the Cerebellum of Mice Repeatedly Exposed to Khat and Treated with β-Lactamase Inhibitor, Clavulanic Acid.Metabolites · 2024Article
- Excitotoxic Storms of Ischemic Stroke: A Non-neuronal Perspective.Molecular neurobiology · 2024Review
- Ceftriaxone and MC-100093 mitigate fentanyl-induced cardiac injury in mice: Preclinical investigation of its underlying molecular mechanisms.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
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Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of glutamate homeostasis is a well-established core feature of neuropsychiatric disorders. Extracellular glutamate concentration is regulated by glutamate transporter 1 (GLT-1). The discovery of a beta-lactam antibiotic, ceftriaxone (CEF), as a safe compound with unique ability to upregulate GLT-1 sparked the interest in testing its efficacy as a novel therapeutic agent in animal models of neuropsychiatric disorders with hyperglutamatergic states. Indeed, more than 100 preclinical studies have shown the efficacy of CEF in attenuating the behavioral manifestations of various hyperglutamatergic brain disorders such as ischemic stroke, amyotrophic lateral sclerosis (ALS), seizure, Huntington's disease, and various aspects of drug use disorders. However, despite rich and promising preclinical data, only one large-scale clinical trial testing the efficacy of CEF in patients with ALS is reported. Unfortunately, in that study, there was no significant difference in survival between placebo- and CEF-treated patients. In this review, we discussed the translational potential of preclinical efficacy of CEF based on four different parameters: (1) initiation of CEF treatment in relation to induction of the hyperglutamatergic state, (2) onset of response in preclinical models in relation to onset of GLT-1 upregulation, (3) mechanisms of action of CEF on GLT-1 expression and function, and (4) non-GLT-1-mediated mechanisms for CEF. Our detailed review of the literature brings new insights into underlying molecular mechanisms correlating the preclinical efficacy of CEF. We concluded here that CEF may be clinically effective in selected cases in acute and transient hyperglutamatergic states such as early drug withdrawal conditions.
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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.