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

Comparison of the Utility of Amplitude-Spectral and Coherence Features of Psychotropic Drugs' Action on ECoG Signal for Pharmaco-EEG Based Drug Screening in Rats. (PubMed, Methods Protoc) - "The training set, relative to which the effects of the pharmacological agents from the test set were classified, were the matrices of effects of 12 pharmacological agents: the NMDA antagonist dizocilpine, the D2/D3 antagonists haloperidol and sulpiride, the M-anticholinergic tropicamide, the H1/5HT2A receptor blocker hydroxyzine, the acetylcholinesterase inhibitor galantamine, the alpha-2 adrenergic agonist dexmedetomidine, the alpha-2 adrenergic antagonist atipamezole, the adenosine receptor blocker caffeine and the GABA-mimetics aminophenylbutyric acid (phenibut), bromdihydrochlorophenylbenzodiazepine (phenazepam) and 5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione. The test set included various drugs with tropism for the targets of the training set drugs: dopamine receptor antagonists chlorpromazine, droperidol, tiapride and raclopride, H1-histamine blockers diphenhydramine and promethazine, 5-HT2-receptor blockers ritanserin and glemenserin, acetylcholinesterase..."

Journal • Preclinical • Pain

Disruption of ultrasonic vocalizations with systemic administration of the non-competitive N-methyl-D-aspartate receptor antagonist MK-801 in adult male mice. (PubMed, Int J Neuropsychopharmacol) - "Systemic MK-801 administration to the male reduced the number of USVs recorded during male-female interactions and produced distinct effects on social approach, locomotor activity, and excretory outcomes. These findings indicate that NMDA receptor blockade differentially affects multiple behavioral domains, although the mechanisms underlying the reduction in USVs remain to be determined."

Journal • Preclinical

Sigma-1 receptor involvement in the paradigm-dependent anti-amnesic effects of multimodal HBK-10 under NMDA receptor hypofunction, with accompanying hippocampal ERK1/2 and BDNF modulation. (PubMed, Biochem Pharmacol) - "Neuroprotection was evaluated in amyloid-β25-35 (Aβ25-35)-exposed SH-SY5Y cells, and cognitive efficacy in MK-801-treated mice using recognition, spatial, and aversive memory paradigms...Behavioral efficacy was accompanied by normalization of hippocampal phosphorylated ERK1/2 (pERK1/2) and increased BDNF after Morris water maze, whereas acute administration did not evoke a detectable ERK1/2 response. These findings indicate that HBK-10 combines sigma-1 receptor engagement with paradigm-dependent anti-amnesic efficacy and post-behavioral changes in hippocampal plasticity-related markers, supporting its further pharmacokinetic and mechanistic characterization as a multimodal compound with potential relevance for cognitive dysfunction associated with disrupted glutamatergic signaling."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Psychiatry • BDNF • HSPA5

Role of superficial grey layer of superior colliculus in reversal learning: importance of nitric oxide synthase. (PubMed, Eur J Pharmacol) - "MK801 caused reversal learning deficits, and we found reduced active lever press activity, while increasing inactive lever presses and locomotor behaviour, indicating impaired reversal learning in rats...Fluoro-ruby retrograde tracing was performed in the VTA, which revealed a possible nitrergic projection from SuG to VTA. We suggest that nNOS signaling in the SuG might play an important role in visual cue-associated reversal learning in rats."

Journal • CASP3 • GFAP

Systematic characterization of subchronic MK-801 administration across mouse strains identifies conserved synaptic alterations and a clear cognitive phenotype in C57BL/6J mice. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Subchronic MK-801 administration produces directionally consistent synaptic alterations across strains and a reliable cognitive phenotype in C57BL/6J mice. These findings provide a practical and tractable framework for selecting and interpreting pharmacological MK-801 models in preclinical schizophrenia research."

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

Ovariectomy reverses maternal immune activation-induced deficits in dopamine and NMDA receptor-mediated regulation of prepulse inhibition in female Long-Evans rats. (PubMed, Schizophr Res) - "In adult female offspring, we measured prepulse inhibition (PPI) and its disruption by acute treatment with the dopamine receptor agonist, apomorphine (APO), and the NMDA receptor antagonist, MK-801, and compared intact controls and intact poly(I:C) offspring with ovariectomised (OVX) controls and OVX poly(I:C) offspring...It is likely that the effect of maternal immune activation on PPI regulation involves a delicate endocrine imbalance, most likely involving altered ovarian steroid hormones levels, the effect of which may be reversed by OVX. These results expand our insight into the possible mechanism of action of novel steroid hormone compounds currently trialled for schizophrenia."

Journal • Preclinical • CNS Disorders • Psychiatry • Schizophrenia

Cannabigerol, a minor phytocannabinoid, prevents behavioral changes induced by psychotomimetic drugs. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "Male Swiss mice received intraperitoneal injections of CBG followed by d-amphetamine (AMPH) or MK-801 and were exposed to different behavioral assays, including the open field, novel object recognition (NOR), social interaction, and prepulse inhibition (PPI) tests. These results suggest that CBG therapeutic profile in behavioral assays. Notably, these benefits were observed at reduced concentrations, indicating that this compound represents a promising candidate for future translational and clinical investigations."

Journal • CNS Disorders • Inflammation • Mood Disorders • Pain • Psychiatry • Schizophrenia

NMDA receptor ablation in medial prefrontal cortex disrupts value updating and reward history integration. (PubMed, Neuropsychopharmacology) - "Using a CRISPR-Cas9 approach to eliminate the obligate GluN1 subunit, we induced NMDAR hypofunction centered on the 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 indicate that prefrontal NMDAR signaling supports key components of value-based decision making, while systemic NMDAR hypofunction engages broader mechanisms that further disrupt the integration of recent experience. This work provides a mechanistic account of how localized and distributed glutamatergic dysfunction contribute to distinct components of reinforcement-learning deficits relevant to schizophrenia."

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

α6GABAA receptors as novel targets for ADHD therapy: A proof-of-concept study in MK-801-treated juvenile mice. (PubMed, Eur J Pharmacol) - "Atomoxetine, an approved ADHD medication, also attenuated ADHD-like phenotypes, although with sedative effects. The therapeutic-like effects of Compound 6 were abolished by intracerebellar microinjection of furosemide, an α6GABAA receptor antagonist, and were absent in Gabra6 (α6-encoding gene)-knockout mice, indicating that positive modulation of cerebellar α6GABAA receptors underlies the observed behavioral improvements. Together, these findings provide proof-of-concept that enhancing cerebellar α6GABAA receptor-mediated inhibition can ameliorate ADHD-relevant behavioral impairments and highlight α6GABAA receptor-selective PAMs as a potential pharmacotherapeutic strategy for ADHD."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

High-Dose MK-801 Attenuated Early TTC-Defined Cortical Injury Even under the Conditions of Suppressed Rapamycin-Sensitive pS6 Signaling during Early Cerebral Ischemia-Reperfusion. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The larger plasma volume observed in the MK-801-treated rats may have contributed to the reduced cortical injury. Therefore, mechanisms other than mTORC1 signaling should be considered in the neuroprotective effects of MK-801 during the early stage of cerebral ischemia-reperfusion."

Journal • Cardiovascular • Reperfusion Injury • MMP2

Integrated transcriptomic and metabolomic analysis unravels the molecular basis of conspecific aggression in Pelodiscus sinensis. (PubMed, Comp Biochem Physiol Part D Genomics Proteomics) - "Drug injection tests demonstrated that NMDA receptor antagonist MK-801 significantly reduced attacks, indicating that glutamatergic signaling is a primary driver of aggressive behavior. These findings highlight conserved excitatory mechanisms in vertebrate aggression with reptile-specific characteristics and offer targets for low aggressiveness breeding in aquaculture."

Journal

Psychoactive drug effects on melanin production and melanocyte gene expression in zebrafish larvae (WFSBP 2026) - "Objective: This study examines how opioid use disorder–related compounds (morphine, MK801, and domperidone) affect melanogenesis and melanocyte gene expression in developing zebrafish (Danio rerio) to determine whether pigmentation biology is altered through pathways relevant to opioid exposure. Opioid use disorder–related compounds significantly modulate pigmentation biology in zebrafish by altering melanin production and melanocyte gene expression. These findings highlight links between opioid-related signaling and melanogenesis, supporting the use of zebrafish as a sensitive model for studying pigmentation changes associated with opioid exposure."

Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse • SOX10

Oligodendrocytes as part of schizophrenia risk (WFSBP 2026) - "Here, I present an integrated view of biochemical mechanisms underlying glial dysfunction based on proteomics analyses of postmortem brain tissue, stem cell–derived models, and pharmacological approaches, including NMDA receptor antagonism (MK-801) and cannabinoid modulation...Importantly, pharmacological interventions targeting these pathways modulate overlapping biochemical networks, suggesting that part of their effects may involve restoration of oligodendrocyte function. This integrative framework supports a shift toward glia-centered models of psychiatric disorders and highlights oligodendrocytes as promising targets for future therapeutic strategies."

CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

Cannabigerol improves MK-801-induced long-term recognition memory deficit in male rats through cortical TrkB-R signaling independently of changes in BDNF. (PubMed, Pharmacol Biochem Behav) - "These results suggest that activation of TrkB-R signaling through a BDNF-independent mechanism may contribute to the preservation of LTM by CBG. Our results provide relevant evidence supporting the therapeutic potential of CBG for cognitive impairments associated with schizophrenia."

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

COMPARISON OF (2R,6R)-HYDROXYNORKETAMINE AND MK-801 PHARMACOLOGICAL EFFICACY TO ATTUNE OPIOID TOLERANCE IN MICE (ASA 2026) - "Abstract is embargoed at this time."

Preclinical • Oncology • Pain

Upregulation of circSUCO22-20 in schizophrenia: clinical correlation with systemic inflammation and in vitro pro-apoptotic mechanisms. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "circSUCO22-20 is upregulated in SCZ and correlates with systemic inflammation. By modulating the hsa-miR-3913-3p/SLC7A11 axis, it exacerbates neuronal apoptosis, supporting its potential as a diagnostic biomarker and therapeutic target for SCZ."

Journal • Preclinical • CNS Disorders • Inflammation • Mental Retardation • Psychiatry • Schizophrenia • SLC7A11

Neuronal mechanisms mediating long-lasting changes in signal processing also influence neurovascular coupling in the rat hippocampus. (PubMed, J Neurosci) - "Pharmacological experiments using MK801 and isoflurane further demonstrated that the mechanisms underlying long-lasting changes in signal processing also enhance LIS-induced BOLD responses. Here, we show that identical inputs can elicit stronger BOLD responses when they also induce long-lasting changes in local network properties, even when the overall activity of principal neurons remains similar. This suggests that the BOLD response is better understood as an indicator of functionally relevant changes in local network processing rather than a purely quantitative measure of neuronal activity."

Journal • Preclinical

Development of glutamatergic antipsychotics requires efficient synaptic glutamatergic transmission while preventing NMDA receptor down-regulation and overactivation of extrasynaptic transmission. (PubMed, Br J Pharmacol) - "These results suggest that potentiation of the NMDA receptor is involved in improving negative symptoms, but down-regulating NMDA receptor and enhanced extrasynaptic-NMDA receptor conversely contribute to the aggravation of negative symptoms."

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

MiR-124 ameliorates MK-801-induced anxiety-like behaviors in mice by promoting hippocampal neural stem cell proliferation and differentiation (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "Hippocampal Tuj1 protein expression and the numbers of hippocampal neural stem cells and newborn neurons, along with the fluorescence area ratio of newborn to mature neurons, increased significantly in the mice in MK-801+miR-124 group. Conclusion miR-124 overexpression ameliorates MK-801-induced anxiety-like behaviors in mice by promoting hippocampal neural stem cell proliferation and differentiation and increasing hippocampal neuron number, suggesting the value of miR-124 as a potential therapeutic target for anxiety disorders."

Journal • Preclinical • CNS Disorders • Mood Disorders • Psychiatry • MIR124-3

Immunohistochemical evidence of glutamatergic modulation of Nesfatin-1 neurons in the rat supraoptic nucleus during inflammatory stress. (PubMed, Tissue Cell) - "Acute inflammatory stress activates Nesfatin-1 neurons in the SON, and this response is modulated by glutamatergic signaling. These findings provide new immunohistochemical evidence linking glutamatergic transmission to stress-induced Nesfatin-1 activation, with potential implications for the neurobiological interaction between inflammation, energy homeostasis, and stress-related processes."

Journal • Preclinical • Inflammation • FOS

Environmental enrichment modulates parvalbumin interneuron deficits and plasticity-related signaling after early postnatal NMDA receptor hypofunction in male rat visual cortex. (PubMed, Brain Struct Funct) - "Here, we examined the effects of early postnatal N-methyl-D-aspartate (NMDA) receptor blockade with MK-801 on the number of PV+ and somatostatin-expressing (SST+) interneurons in the primary visual cortex (V1) and assessed whether environmental enrichment (EE) in adulthood modulates these alterations by analyzing molecular changes using Western blot...These findings indicate that early NMDA receptor hypofunction induces long-lasting, subtype-specific alterations in inhibitory circuitry in V1. EE in adulthood engages molecular pathways associated with synaptic plasticity and modulates interneuron immunoreactivity, suggesting that inhibitory circuits retain some capacity for experience-dependent remodeling despite persistent receptor-level deficits."

Journal • Preclinical • CNS Disorders • Psychiatry • Schizophrenia • DLG4

Transcranial focused ultrasound stimulation in schizophrenia: current evidence, mechanisms, and future directions. (PubMed, Front Psychiatry) - "In dizocilpine (MK-801) rodent models, tFUS has been reported to reverse cognitive deficits, prevent psychotic-like behaviors, restore parvalbumin-positive GABAergic interneuron markers in the prefrontal cortex, and upregulate NMDA receptor-related signaling...Preclinical and early clinical studies suggest that tFUS may have therapeutic potential in schizophrenia, but current evidence is insufficient to support definitive clinical conclusions. Larger well-controlled studies are required."

Journal • Review • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Bisphenol S Disrupts Neuronal Morphogenesis in Human Neural Cells by Overactivating NMDA Receptor-Ca2+ Signaling. (PubMed, Food Chem Toxicol) - "Using a three-stage human embryonic stem cell (hESC-H9) neural differentiation model, cells were exposed to 375 μM BPS, 375 μM BPS + 5 μM NMDAR inhibitor (MK801), 375 μM BPS + 5 μM ERK pathway inhibitor (U0126), and a 0.1% DMSO solvent control, respectively...ERK is activated downstream but independently regulates neuronal morphology rather than serving as a linear executor of NMDAR-driven toxicity. Collectively, NMDAR is the pivotal mediator of BPS neurotoxicity, and the NMDAR-ERK axis involves both convergent and divergent mechanisms, underscoring the need for stage-specific neuroprotective strategies."

Journal • BDNF

Detecting drug-induced EEG alterations with machine learning: A methodological proof-of-concept study in rats treated with MK-801. (PubMed, J Pharmacol Toxicol Methods) - "These findings support the feasibility of using deep learning to detect compound-related EEG alterations in low-channel rat recordings with limited preprocessing. Two complementary forms of generalization were assessed: transfer to unseen treatment conditions within known subjects in the crossover setting, and generalization to entirely unseen animals in the leave-one-subject-out (LOSO) setting. The lower LOSO performance is consistent with the more stringent validation conditions. Together, these results suggest that the approach may complement conventional analytical pipelines and support more automated, standardized preclinical EEG workflows for both safety and efficacy pharmacology studies."

Journal • Preclinical

Pairing ampakine with brief hypoxia evokes phrenic neuroplasticity via a spinal NMDA receptor mediated mechanism. (PubMed, Function (Oxf)) - "Pairing ampakine CX717 with brief moderate or severe hypercapnia failed to produce pMF. Pairing doxapram, a respiratory stimulant, with hypoxia did not produce pMF...In contrast, the NMDA-R blocker MK-801 prevented pMF when administered before but not after A-H...We conclude that the mechanism driving sustained increases in phrenic motor output after A-H is independent of spinal adenosine or serotonin receptor activation, but requires spinal NMDA-R activation for the induction, but not maintenance of A-H pMF. Ampakine pretreatment may be useful to increase the efficacy of hypoxia-based rehabilitation paradigms after SCI, particularly since clinical trials report a substantial number of "low-responders"."

Journal • Anesthesia • CNS Disorders • Orthopedics