dizocilpine (MK801) / Merck (MSD) - LARVOL DELTA

Impulsivity in NrCAM KO Mice Is Reduced by NMDAR Antagonist MK-801 but Not by AMPAR Antagonist CNQX. (PubMed, NeuroSci) - "In NrCAM KO mice, a low dose of MK-801 decreased neuronal activation in the ventral orbitofrontal cortex and increased activation in the accumbens shell and core. These results indicate differential effects of genotype, stress, and response to glutamatergic drugs and support a role for NrCAM in stress-induced behavioral alterations relevant to addiction and psychiatric disorders."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

RELATIONSHIPS AMONG TAU, AMYLOID, NEUROINFLAMMATION AND NMDA RECEPTOR MARKERS VARY BY SEX, REGION, AND ALZHEIMER'S DISEASE STAGE (ADPD 2026) - "Cryostat sections were processed for quantitative autoradiography of tau, amyloid beta, TSPO (neuroinflammation marker), and NMDA receptors using [18F]T807, [3H]Pib, [3H]PK11195 and [3H]MK801, respectively... The relationship among tau deposition, amyloid burden, neuroinflammation and NMDA receptor density is strongly modulated by sex, region and Alzheimer's disease stage."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation

Comparative EEG analysis of the effects of ketamine enantiomers and metabolites in rhesus macaques. (PubMed, J Neurophysiol) - "This study compared the effects of (R)-ketamine, (S)-ketamine, their metabolites, and another N-methyl-D-aspartate antagonist, MK-801, on the electroencephalograms (EEGs) of rhesus macaques across a wide range of doses...This comprehensive EEG evaluation in a non-human primate, together with measurements of plasma drug concentrations, when interpreted in comparison with existing clinical data, provide increased translational insight into the dose-dependent neurophysiological characteristics of (R,S)-ketamine, its enantiomers and metabolites. EEG-based comparisons of (R)-ketamine with (R,S)-ketamine and (S)-ketamine suggest that (R)-ketamine exhibits neurophysiological features consistent with a potentially broader therapeutic range for antidepressant effects."

Journal • Anesthesia • CNS Disorders • Depression • Psychiatry

Differential effects of cariprazine, LY379268 and donepezil on EEG oscillations and auditory steady-state response in MK-801-treated rats: relevance for schizophrenia drug development. (PubMed, Neuropharmacology) - "These results highlight shed new lights on potential pharmacological strategies focused on circuits dysfunction andsymptoms in SZ. These differential normalization profiles, including cariprazine's unique broad-spectrum signature, reveal distinct patterns of circuit engagement and provide a translational pharmaco-EEG framework for circuit-level target engagement in SZ drug development."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Task-Specific Effects of mGlu2/3 Receptor Agonist LY379268 on MK-801-Induced Behavioral and Neural Dysfunctions in Rats. (PubMed, Physiol Res) - "Electrophysiological recordings revealed that MK-801, alone or in combination with LY379268 (1 mg/kg), disrupted theta-high gamma phase-amplitude coupling in the open field test, indicating impaired neural processing. This complexity underscores the need for further research to refine the therapeutic potential of mGlu2/3 modulation in conditions associated with glutamatergic dysfunction. Key words MK-801 " LY379268 " Electrophysiology " Medial prefrontal cortex " Hyperlocomotion."

Journal • Preclinical • Anesthesia • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

A spatiotemporally controlled MNE@PDA-Diz/GP hydrogel system: enhancing spinal cord injury repair via ROS scavenging, calcium influx inhibition, and macrophage polarization. (PubMed, RSC Adv) - "These three components work in synergy: the manganese nanozyme scavenges reactive oxygen species to exert anti-oxidative effects, polydopamine modulates macrophage polarization to alleviate inflammation, and dizocilpine inhibits calcium influx to provide neuroprotection. This work presents a novel and versatile platform for multi-targeted SCI therapy and promotes the development of regenerative strategies."

Journal • CNS Disorders • Inflammation • Orthopedics

TAAR1-mediated pathways regulating nigrostriatal function and the discovery and pharmacological characterization of a novel TAAR1 agonist, Selutaront. (PubMed, Front Pharmacol) - "We evaluated its antipsychotic-like effects in a mouse model similar to schizophrenia induced by MK-801 and identified its potential mechanism...This study demonstrates that TAAR1 regulates nigrostriatal function primarily via the PKA/CREB/DARPP32 signaling axis. Selutaront, a novel highly selective TAAR1 agonist with favorable drug-like properties, represents a promising candidate for schizophrenia treatment and provides mechanistic insights into TAAR1-targeted therapy."

Journal • CNS Disorders • Developmental Disorders • Psychiatry • Schizophrenia

Interaction between transient receptor potential vanilloid 4 and glutamate NMDA receptor subunit 1 mediates endoplasmic reticulum stress and neuroinflammation in postoperative delirium. (PubMed, Mol Biomed) - "Inhibiting NMDAR with MK801 recapitulated these therapeutic benefits. Furthermore, TRPV4 was significantly upregulated in early-onset Alzheimer's disease patients. Our study defines a novel TRPV4-GluN1 axis that drives POD pathogenesis, suggesting that it is a promising therapeutic target."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • ATF6 • CA3 • ICAM1 • IL1B • IL6 • TRPV4

Pharmacological dissociation between transient auditory evoked response and the 40 Hz auditory steady state response. (PubMed, Neuroscience) - "We tested two compounds, MK-801 and clozapine, which are known to modulate the 40 Hz response in opposite directions. We further speculate that transient responses such as tone-evoked N1 are primarily driven by rapid feedforward transmission, whereas 40 Hz oscillations emerge from recurrent network activity that builds up gradually. Their established cross-species translational utility and strong but uncorrelated pharmacological responsiveness establish the two measures as largely independent pharmacodynamic biomarkers for drug development."

Journal

Protective effects of a highly water-soluble rutin on cognitive dysfunction in mice. (PubMed, J Pharmacol Sci) - "The oral administration of wsRutin solution significantly improved scopolamine- and MK-801-induced cognitive impairment in the novel object recognition test. wsRutin solution also enhanced the expression of brain-derived neurotrophic factor (BDNF)-related proteins in the hippocampus, including BDNF pro-peptide, p-TrkB, p-CREB, PKCα, NR1, HO-1 and NQO1. These findings suggest that wsRutin improves cognitive function via activating BDNF/TrkB signaling or antioxidant mechanism and may represent a preventive agent for dementia."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • NQO1

Clocking Stroke: A Systematic Review of Circadian Biology Governing Ischemic Risk and Therapeutic Efficacy (AAN 2026) - "Injury is time-dependent, linked to circadian control involving neuroprotection by agents (αPBN, MK-801), RORalpha for melatonin-mediated reperfusion protection, Bmal1-driven angiogenesis, and Smyd-2-regulated cell death... Circadian biology is a critical, actionable factor of stroke pathophysiology. Our findings suggest integrating patient-specific chronotype assessment, diagnostic assessments (e.g., Hcrt-1), and circulating biomarkers is crucial for precision chronotherapy, enabling personalized treatments that improve neuroprotection and thereby maximizing functional neurological outcomes."

Clinical • Review • Cardiovascular • CNS Disorders • Ischemic stroke • Vascular Neurology • ARNTL • BMAL1

Structure-activity optimization of N-arylindole GPR52 agonists for enhanced antipsychotic efficacy: design, synthesis, and pharmacological evaluation. (PubMed, RSC Med Chem) - "Among them, three compounds (H11, H20, H26) exhibited good GPR52 potency and inhibition rates in the MK-801-induced hyperlocomotion model, with ED50 values of 6.18-6.92 mg kg-1...Molecular docking confirmed stable binding interactions with GPR52's "bird's claw" pocket, while ADMET predictions supported favorable drug-like properties. These designed small molecules will facilitate the development of novel GPR52 agonists."

Journal • CNS Disorders • Psychiatry • Schizophrenia • GPR52

NMDA receptor antagonism requires serotonin and noradrenaline to induce antidepressant-like effects in a treatment-resistant depression rat model. (PubMed, Eur J Pharmacol) - "Thus, independent groups of Wistar Kyoto Rats were administered MK-801 alone or with desipramine or sertraline, and then evaluated in the open field and the forced swimming test (FST). In conclusion, MK-801 may enhance the effect of classical antidepressants in treatment-resistant models. Moreover, NMDA receptor antagonism relies on the integrity of the serotonergic and noradrenergic systems to exert antidepressant-like effects."

Journal • Preclinical • CNS Disorders • Depression • Mood Disorders • Psychiatry

The effects and mechanisms of baicalin on MK-801 induced schizophrenia model mice. (PubMed, Technol Health Care) - "Staining confirmed BA reduced cerebral oxidative stress/neuroinflammation. Western blot showed dose-dependent elevation of p-Akt/Akt and p-GSK3β/GSK3β ratios.ConclusionBaicalin may improve cognitive impairments in MK801-induced schizophrenia model mice through the PI3K/Akt/GSK3β signaling pathway, exhibiting anti-neuroinflammatory and neuroprotective effects."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Pain • Psychiatry • Schizophrenia • IL1B • IL6 • TNFA

The impact of predator stress on electroshock seizure threshold: insights into GABAergic, glutamatergic, and serotonergic pathways in mice. (PubMed, Behav Brain Funct) - "This study shows that predator stress is associated with increased seizure susceptibility and with downregulation of hippocampal GABAAα1R and 5-HT1AR expression, together with enhanced NF-κB activation and reduced ERK signaling. Pharmacological modulation of GABAergic, glutamatergic, and serotonergic pathways reversed the stress-induced reduction in seizure threshold in this model, suggesting that these systems may contribute to stress-related seizure susceptibility."

Journal • Preclinical • CNS Disorders • Epilepsy • Mood Disorders • Post-traumatic Stress Disorder

N-methyl-D-aspartate receptor inhibition protects against obesity-induced kidney disease. (PubMed, Nephrol Dial Transplant) - "Our results demonstrate that renal NMDAR contributes to the pathogenesis of OIKD and underscore the therapeutic potential of targeting this receptor to attenuate inflammation and kidney injury in obesity-associated nephropathy."

Journal • Chronic Kidney Disease • Genetic Disorders • Inflammation • Nephrology • Obesity • Renal Disease

A Human Cortical Tissue Platform for High-Throughput Screening of Ischemic Injury Therapeutics (ISC 2026) - "To illustrate a high-throughput screening mode, samples were treated with free radical scavenger, Astaxanthin (AST; 1, 10, 50 mM), excitotoxicity antagonist, MK801 (1, 10, 100 mM), antioxidant enhancer, oltipraz (OLT; 1, 10, 100 mM), and pan-caspase inhibitor, ZVAD-fmk (1, 10, 50 mM). ZVAD-fmk reduced the ratio for 1, 10, 50 mM to 0.123, 0.046, 0.00 (all p<0.001), respectively.This novel method of determining treatment success in a high-throughput mode allowed us to evaluate five treatment groups with three doses per drug treatment using a single human cortical tissue resection specimen. This method can be adapted for screening additional research interests involving the cellular biological response of human cortical tissue."

Cardiovascular • Inflammation • Reperfusion Injury • CD31 • GFAP • PECAM1

Glutamate load fosters spreading depolarization under osmotic stress in brain slices. (PubMed, Front Cell Neurosci) - "Astrocyte swelling was reduced by blocking AQP4+NKCC1 (TGN-020 + bumetanide) and VRAC channels (DCPIB), while neuronal NMDA and AMPA/kainate receptors were antagonized with MK-801 + CNQX. Both astrocytic and neuronal interventions disrupted typical SD initiation patterns, producing atypical, multifocal SD events. These findings demonstrate that astrocyte volume regulation and neuronal ionotropic glutamate receptors jointly shape SD characteristics under osmotic stress, identifying astrocytic water/ion homeostasis and glutamatergic signaling as potential therapeutic targets to limit excitotoxic injury in acute cerebrovascular disease."

Journal • Cardiovascular • CNS Disorders • Ischemic stroke • Vascular Neurology

Antidepressant-Related Signaling Pathways of Zinc Oxide Nanoparticles in a Mouse Model of Postpartum Depression. (PubMed, Biol Trace Elem Res) - "PPD was induced in female mice via intraperitoneal injection of progesterone (5 mg/kg) for 5 days, followed by 3 days withdrawal period. Pre-treatment with L-NAME, adenosine, and MK-801 amplified the decrease in immobility duration provoked by a sub-effective dose of ZnO NPs. These findings suggest that the antidepressant-like action of ZnO NPs is likely mediated through nitrergic, serotonergic, adenosinergic, and glutamatergic pathways."

Journal • Preclinical • CNS Disorders • Depression • Mental Retardation • Mood Disorders • Postpartum Depression • Psychiatry

Chemogenetic Modulation of Prefrontal Cortex Influences Auditory Cortex Responses and Event-Related Potentials in a Schizophrenia Rat Model (ARO 2026) - "We first carried out the recordings in a control condition, then alternated one week with 8 days of MK-801 (0.1 mg/Kg, IP), followed by one week of washout, and the same for MK-801 (0.2 mg/Kg). Our results show that NMDAR dysfunction induces an alteration of the AC LFP and on the event-related potential components. The C21 infusion into PFC-L increased the amplitude of the AC-L deviant response, an effect that was not present during saline infusion. This suggests that the absence of a top-down PFC predictions, the prediction error increases in AC."

Preclinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Auditory Novelty Detection Impairment in Rats Treated With the Nmda Receptor Antagonist MK-801: A Model of Schizophrenia (ARO 2026) - "These findings suggest that NMDA receptor blockade with MK-801 disrupts auditory novelty detection at both behavioral and neural levels. This pharmacological model provides valuable insights into the mechanisms underlying sensory and cognitive deficits in schizophrenia. Supported by project PID2023-148541OB-I00, funded by MICIU/ AEI https://doi.org/10.13039/501100011033 and FEDER EU."

Preclinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Differential effects of orexin system activation on dizocilpine-induced schizophrenia-like behaviors in mice. (PubMed, Neuropeptides) - "However, substantial variability across assays, potentially related to the dosing of dizocilpine, orexin A, and CNO, as well as protocol-dependent constraints in some behavioral paradigms, limits definitive interpretation. Nevertheless, the present data reveal novel and domain-specific effects of orexin signaling in schizophrenia-relevant behavioral circuits and highlight the importance of exploring interventions with intermediate efficacy, including newly emerging orexin receptor agonists, to more precisely delineate orexin-dependent mechanisms and their therapeutic potential for negative and cognitive symptom domains."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Psychiatry • Schizophrenia

PHARMACOLOGICAL ACTIVITY OF A NEW LIGAND BINDING AT THE HISTAMINE SITE OF THE NMDA RECEPTOR IN RODENTS. (PubMed, Eur J Pharmacol) - "FUBn293 (10 mg/kg i.p.) significantly reduced the conditioned active avoidance test response and suppressed the MK-801-induced prepulse inhibition deficit. According to these findings, NMDA(HA)R agonists may offer a novel class of antipsychotic medications for the treatment of some aspects of schizophrenia and other neurological or psychiatric disorders."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

RhoA regulates morphine associated NMDA receptor signaling in the prelimbic region of medial prefrontal cortex pyramidal neurons. (PubMed, Brain Res) - "In vitro whole-cell patch-clamp recordings of layer 5 neurons, stimulated at layer 2/3, revealed that Rhosin reduced the amplitude of synaptic NMDAR-mediated excitatory postsynaptic currents. Additionally, using an activity-dependent MK-801 block to isolate extrasynaptic components, we demonstrated that RhoA inhibition significantly attenuated extrasynaptic NMDAR activation, likely by limiting glutamate spillover during high-frequency stimulation. These findings elucidate a critical mechanism by which RhoA mediates opioid-induced neuroadaptations through the regulation of both synaptic and extrasynaptic NMDAR activity, identifying RhoA in the PLC as a promising therapeutic target for opioid dependence."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • RHOA

NMDA receptor ablation in medial prefrontal cortex disrupts value updating and reward history integration. (PubMed, bioRxiv) - "Using a CRISPR-Cas9 approach to eliminate the obligate GluN1 subunit, we induced spatially confined NMDAR hypofunction in mPFC and compared its effects to systemic pharmacological blockade with the NMDAR antagonist MK-801 during performance of a touchscreen-based restless bandit task...Together, these findings demonstrate that prefrontal NMDAR signaling is necessary for effective value updating and feedback-driven learning, and that its loss recapitulates core features of systemic NMDAR hypofunction. This work establishes a mechanistic bridge between localized cortical glutamatergic dysfunction and the reinforcement-learning disturbances characteristic of schizophrenia."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia