Endogenous antagonists of <i>N</i>‐methyl‐<scp>d</scp>‐aspartate receptor in schizophrenia

Jorratt, Pascal; Höschl, Cyril; Ovsepian, Saak V.

doi:10.1002/alz.12244

Cited by 19 publications

(17 citation statements)

References 191 publications

(207 reference statements)

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“…(3) the agonist glutamate, and co-agonists (glycine, D-serine; Jorratt et al, 2021). In addition, the expression and function of NMDAR are also affected by the expression and transcription process of related NMDAR genes, microRNAs, related proteins, and signaling pathways.…”

Section: The Regulation Of Nmdar In Epilepsymentioning

confidence: 99%

“…The NMDAR ion channel pores are permeable to Ca 2+ but can be blocked by Magnesium ion (Mg 2+ ) in a strongly voltagedependent manner, which makes them largely inactive at resting voltages, even in the presence of agonists (Mayer et al, 1984;Nikolaev et al, 2021). Activation of the NMDAR is a cooperative process, which depends on the relief of the Mg 2+ block of the ion channel pore (Mg 2+ is removed into the extracellular compartment from the channel pore; Hou et al, 2020;Jorratt et al, 2021). The NMDAR channel is blocked by Mg 2+ at neuronal resting membrane potential, and Mg 2+ is removed when the membrane is depolarized (Jorratt et al, 2021;Li et al, 2021).…”

Section: Magnesium (Mg)mentioning

confidence: 99%

“…Activation of the NMDAR is a cooperative process, which depends on the relief of the Mg 2+ block of the ion channel pore (Mg 2+ is removed into the extracellular compartment from the channel pore; Hou et al, 2020;Jorratt et al, 2021). The NMDAR channel is blocked by Mg 2+ at neuronal resting membrane potential, and Mg 2+ is removed when the membrane is depolarized (Jorratt et al, 2021;Li et al, 2021). In addition, non-competitive NMDAR ion channel blockers such as MK-801 mainly bind to ion channels of TMD.…”

Section: Magnesium (Mg)mentioning

confidence: 99%

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Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Chen

Liu

et al. 2022

Front. Mol. Neurosci.

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Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

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Section: The Regulation Of Nmdar In Epilepsymentioning

confidence: 99%

Section: Magnesium (Mg)mentioning

confidence: 99%

Section: Magnesium (Mg)mentioning

confidence: 99%

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Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Chen

Liu

et al. 2022

Front. Mol. Neurosci.

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“…On the one hand, PAs can enhance NMDA receptor currents by increasing the probability of channel opening. On the other hand, spermine is able to block NMDA channels in the open state, thereby reducing or blocking NMDA receptor currents by a voltage-dependent reduction of single-channel conductance[ 34 , 35 ]. Another inhibitory effect of spermine is to reduce the sensitivity to glutamate (or other glutamate site agonists) at NMDA receptors composed of NMDA receptor 1/NMDA receptor 2B subunits by reducing the affinity for glutamate[ 34 ].…”

Section: Some Critical Functions Of Pa In the Cns At A Glancementioning

confidence: 99%

“…On the other hand, spermine is able to block NMDA channels in the open state, thereby reducing or blocking NMDA receptor currents by a voltage-dependent reduction of single-channel conductance[ 34 , 35 ]. Another inhibitory effect of spermine is to reduce the sensitivity to glutamate (or other glutamate site agonists) at NMDA receptors composed of NMDA receptor 1/NMDA receptor 2B subunits by reducing the affinity for glutamate[ 34 ]. PAs also contribute to alterations of membrane excitability by interacting with ionotropic kainate and AMPA glutamate receptors (discussed in detail in[ 36 ]).…”

Section: Some Critical Functions Of Pa In the Cns At A Glancementioning

confidence: 99%

Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Bernstein¹,

Keilhoff²,

Laube³

et al. 2021

WJP

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Polyamines play preeminent roles in a variety of cellular functions in the central nervous system and other organs. A large body of evidence suggests that the polyamine pathway is prominently involved in the etiology and pathology of schizophrenia. Alterations in the expression and activity of polyamine metabolizing enzymes, as well as changes in the levels of the individual polyamines, their precursors and derivatives, have been measured in schizophrenia and animal models of the disease. Additionally, neuroleptic treatment has been shown to influence polyamine concentrations in brain and blood of individuals with schizophrenia. Thus, the polyamine system may appear to be a promising target for neuropharmacological treatment of schizophrenia. However, for a number of practical reasons there is currently only limited hope for a polyamine-based schizophrenia therapy.

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Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery

Chen,

Guo,

et al. 2024

JAMA Netw Open

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ImportancePostpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant.ObjectiveTo investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD.Design, Setting, and ParticipantsA single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis.InterventionsPatients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients.Main Outcomes and MeasuresThe primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42.ResultsA total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], −1.17 [0.44]; 95% CI, −2.04 to −0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03).Conclusions and RelevanceThese results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores.Trial RegistrationChinese Clinical Trial Registry Identifier: ChiCTR2100054199

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Endogenous antagonists of N‐methyl‐d‐aspartate receptor in schizophrenia

Cited by 19 publications

References 191 publications

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery

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