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

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

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

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

Neurophysiological and neuropharmacological effects of melatonin MT2 receptors activation in MK-801-induced schizophrenia-like dysfunctions. (PubMed, Biochem Pharmacol) - "These findings indicate that MT2 receptor stimulation selectively enhances prefrontal inhibitory tone and ameliorates behavioral abnormalities related to positive-like and negative-like symptoms, without normalizing cognitive and electrophysiological deficits. Overall, MT2 receptor-selective drugs may represent promising candidates for targeting specific symptom domains in SCZ through mechanisms distinct from current antipsychotics."

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

Non-invasive modulation of brain activity and behavior by transcranial radio frequency stimulation. (PubMed, Brain Stimul) - "TRFS represents a conceptual advance in neuromodulation, uniting the inherent capability of RF energy to target deep brain tissue with the biophysical reliability of thermal modulation. TRFS applications are bimodal, capable of influencing the pristine brain by suppressing the activity of specific neuronal populations in targeted regions, or of exciting selectively transfected neural ensembles expressing thermosensitive TRPV1 ion channels. The latter modality, first introduced here, represents a novel concept termed "RF-genetics." TRFS represents a promising platform for next-generation non-invasive brain stimulation with potential translational applications in treating various neurological and psychiatric disorders."

Journal • CNS Disorders • Mental Retardation • Psychiatry

Negr1 deficiency alters glutamate signalling and kynurenine pathway in a mouse model of psychiatric disorders. (PubMed, Sci Rep) - "Male and female wild-type and Negr1-deficient mice received daily injections of MK-801, a non-competitive NMDA receptor antagonist, until behavioural tolerance developed in the open field test (after 9 days in males and 5 days in females)...Additionally, kynurenine pathway metabolites showed genotype- and sex-dependent alterations. These findings suggest that NEGR1 protein modulates NMDA receptor function and tryptophan metabolism in a sex-dependent manner, highlighting the importance of considering both genetic background and sex in models of glutamatergic dysfunction relevant to neuropsychiatric disorders."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry

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

Investigating the role of melanocortinergic, glutamatergic and neuropeptide Y systems on hypophagia caused by gastric inhibitory polypeptide (GIP) in broilers. (PubMed, Poult Sci) - "This anorexigenic effect of GIP was significantly attenuated by the co-infusion of either the MC3/MC4 receptor antagonist SHU9119 (P < 0.05) or the NMDA receptor antagonist MK-801 (P < 0.05). The collected data imply that signaling cascades dependent on NMDA and melanocortin (MC3/MC4) receptors potentially mediate the anorectic effect of GIP in neonatal broilers, a process which appears independent of NPY Y1, Y2, and Y5 receptor involvement."

Journal

Drug Development. (PubMed, Alzheimers Dement) - "The findings suggest a functional interaction between the muscarinic cholinergic and dopaminergic/NMDA systems in modulating recognition memory. Muscarinic cholinergic agonists, such as xanomeline, may hold therapeutic potential for treating cognitive impairments associated with psychotropic drug abuse."

Journal • Alzheimer's Disease • Cognitive Disorders

Biomarkers. (PubMed, Alzheimers Dement) - P1 | "Results from the non-clinical studies suggest SUVN-I6107 may have memory enhancing property in various forms of dementias. SUVN-I6107 is currently being studied in a Phase-1 study (NCT06705088) to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamic effects after single and repeated administrations in healthy human subjects."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • APP

Non-invasive modulation of brain activity and behavior by transcranial radio frequency stimulation. (PubMed, bioRxiv) - "Behavioral effects were assessed through a rotational test in freely moving mice after MK-801-induced hyperlocomotion...TRFS applications are bimodal, capable of influencing the pristine brain by suppressing the activity of specific neuronal populations in targeted regions, or of exciting selectively transfected neural ensembles expressing thermosensitive TRPV1 ion channels. The latter modality, first introduced here, represents a novel concept termed "RF-genetics." TRFS represents a promising platform for next-generation non-invasive brain stimulation with potential translational applications in treating various neurological and psychiatric disorders."

Journal • CNS Disorders • Mental Retardation • Psychiatry

The Effect of Exposure to Music on Spatial Learning and Memory in Rats. (PubMed, Noro Psikiyatr Ars) - "For the remaining two groups, one was injected with ketamine and the other was injected with MK-801. The effect of music on NMDARs may be at levels that do not change PPI values. Considering that parameters like the duration and intensity of music may cause stress, repeating the experiment with different conditions may provide new clues."

Journal • Preclinical

Association Between Gene Polymorphisms of RSPO2 of the Wnt Signaling Pathway and Schizophrenia in the Korean Population. (PubMed, Psychiatry Investig) - "The findings indicate that RSPO2 gene polymorphisms, particularly rs374810 and rs423940, may contribute to schizophrenia susceptibility. Therefore, RSPO2 expression may be associated with the susceptibility to schizophrenia in the Korean population."

Journal • CNS Disorders • Psychiatry • Schizophrenia • RSPO2

The nitric oxide synthase inhibitor 7-nitroindazole attenuates social withdrawal and memory impairments induced by Blockade of the NMDA receptor in the rat. (PubMed, Psychopharmacology (Berl)) - "The present results indicate that 7-NI is sensitive to glutamate blockade since it decreased behavioural impairments resembling the negative symptoms and cognitive deficits of schizophrenia. Moreover, these findings corroborate the potential of 7-NI as an adjunctive molecule for the medication of schizophrenia."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia • NOS1

Transcriptomic analysis reveals pathway-specific targets for hyperlocomotion and social withdrawal in mouse models of schizophrenia. (PubMed, Neuroscience) - "Differentially expressed genes in the MK-801 model displayed a modest correlation with that of schizophrenia patients (r = 0.40, p = 2.7 × 10-6), higher than the MAM model (r = 0.15, p = 0.23), underscoring NMDAR antagonism's relevance to the core pathology of the disorder. Using weighted gene co-expression network analysis, we identified 28co-expression modules across the mouse models, with 11modules significantly associated with individual schizophrenia-related behavioral endophenotypes.Notably, the brown module (linked to hyperlocomotion, r = 0.55, p = 0.01) and the darkgrey module (associated with social withdrawal, r = -0.71, p = 3 × 10-4)were enriched in Wnt and PI3K/Akt signaling pathways, respectively.Pharmacological inhibition of these two pathways specifically rectified corresponding behavioral anomalies in the MK-801 model, highlighting the critical role of altered Wnt and PI3K/Akt signaling in these behavioral domains of schizophrenia-related..."

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

Exploring effects of chronic d-cycloserine administration on expression of GluN2 subunits and tripartite synaptic transmission in thalamocortical pathway. (PubMed, Br J Pharmacol) - "Chronic d-cycloserine (25 μM and 2 mg·kg-1) down-regulated GluN2C without affecting GluN2A/GluN2B but increased GluN2-related astroglial l-glutamate/d-serine release. Higher d-cycloserine dose (>60 μM; >5 mg·kg-1) inactivated GluN2C, but increased GluN2A related astroglial release. These results indicate that dose-dependent activation and inactivation of GluN2C by d-cycloserine is possibly involved in its efficacy on negative symptom of schizophrenia, but with a narrow therapeutic window."

Journal • CNS Disorders • Depression • Psychiatry • Schizophrenia • GRIN2A • GRIN2B

Functional Characterization and Expression Patterns of novel_circ_037817 in Schizophrenia Patients. (PubMed, Mol Neurobiol) - "Under MK-801 treatment conditions, knockdown of novel_circ_037817 expression increased cell viability, inhibited apoptosis, increased Bcl-2 expression, and reduced Bax expression. In summary, this study provides the first evidence that novel_circ_037817 may be involved in SCZ and offers a novel target for SCZ intervention."

IO biomarker • Journal • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • BCL2 • IL1B • TNFA

A zebrafish model of benzodiazepine-refractory status epilepticus for whole organism discovery of novel anti-seizure treatments (AES 2025) - "The pharmacology of PXN-related SE was probed using inhibitors of NMDAR (MK801) and brain-specific alpha7 nicotinic AChRs (MLA); a positive allosteric modulator of GABAR (diazepam, DZP); and the antidote atropine + 2-pralidoxime (A/2PAM). We show that PXN has LD50(6 hours)= 125uM and at earlier timepoints results in immobility, L-bend contracture, and dramatic brain region-specific increases in tonic calcium fluorescence in still living fish, consistent with status epilepticus. Similar to rodent models of PXN-related SE, our study confirms the key roles of NMDAR and central effects of cholinergic excess to PXN-related SE in zebrafish, as well as its poor response to benzodiazepine treatment. To the best of our knowledge, no existing zebrafish models of seizures demonstrate benzodiazepine resistance. These findings will now enable high-throughput screening to identify novel counter-measures that may control refractory SE related to organophosphate exposure and other..."

CNS Disorders • Epilepsy

Ketamine reduces microglial activation and brain monocyte infiltration and promotes peripheral regulatory immune cells, relieving lipopolysaccharide (LPS)-induced depressive-like behavior in mice. (PubMed, Mol Psychiatry) - "Finally, we showed that the anti-inflammatory and antidepressant effects are linked, perhaps as convergent outcomes, by using another NMDA receptor antagonist, MK-801, and the mTOR signaling inhibitor, rapamycin. These findings highlight ketamine's multifaceted mechanisms of action, underscoring its potential as a treatment for MDD, particularly in patients with significant inflammation."

Journal • Preclinical • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mood Disorders • Psychiatry • CD69 • HAVCR2 • MRC1