Epilepsy is a neurological disease affected by an imbalance of inhibitory and excitatory signaling in the brain.
In this disease, the targets are active in pathophysiology and thus can be used as a focus for pharmacological treatment.
Several studies demonstrated the antiepileptic effect of drugs acting on the following targets: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, voltage-gated calcium channel (Cav), Gamma aminobutyric acid transporter type 1 (GAT1), voltage-gated sodium channels (Nav), voltage-gated potassium channel of the Q subfamily (KCNQ) and Gamma aminobutyric acid type A (GABAA) receiver.
These studies highlight the importance of molecular docking.
Quantitative Structure-Activity Relationship (QSAR) and computer aided drug design (CADD) in predicting of possible pharmacological activities of these targets.

Levodopa is the standard treatment for Parkinson\'s disease, but its use is marred by the emergence of dyskinesia, for which treatment options remain limited. Here, we review the glutamatergic modulators that were assessed for their antidyskinetic potential in clinical trials, including N-methyl-D-aspartate (NMDA) antagonists, agonists at the glycine-binding site on NMDA receptors, metabotropic glutamate (mGlu) 4 agonists, mGlu5 antagonists, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonists and glutamate release inhibitors. Several agents that were investigated are not selective for their targets, raising uncertainty about the extent to which glutamatergic modulation contributed to their effects. Except for amantadine, the use of glutamatergic modulators for the treatment of dyskinesia in Parkinson\'s disease remains largely investigational, with promising results obtained with mGlu5 negative allosteric modulation.
Long-term treatment of Parkinson’s disease results in abnormal involuntary movements called ‘dyskinesia’. The chemical substance ‘glutamate’ is deeply involved in the normal functioning of the brain and the drug amantadine, which is used in the clinic to alleviate dyskinesia, is believed to elicit its effects through modulation of glutamate within the brain. In addition to amantadine, several drugs that interact with glutamate have been tested in the clinic, with variable efficacy. Here, we aim to review the pharmacological mechanisms of these drugs and to discuss their efficacy, or lack thereof, in the treatment of dyskinesia in Parkinson’s disease.

While altered expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type receptor has been reported in postmortem studies of schizophrenia, these findings are inconsistent. Therefore, we aimed to systematically review postmortem studies that investigated AMPA receptor expressions in schizophrenia.
A systematic literature search was conducted for postmortem studies that measured AMPA receptor subunit expressions or receptor bindings in schizophrenia compared to healthy individuals on February 3, 2021, using Medline and Embase.
A total of 39 relevant articles were identified from 1360 initial reports. The dorsolateral prefrontal cortex (DLPFC) was the most investigated region (15 studies), followed by the medial temporal lobe (8 studies). For the DLPFC, 4/15 studies (26.7%) showed increased AMPA receptor binding or subunit expression in patients with schizophrenia compared to that in controls, especially in GRIA1 and GRIA4, 2/15 studies (13.3%) reported a decrease, particularly in GRIA2, and 8/15 studies (56.7%) found no significant differences. A decreased expression or receptor binding was observed in 6/8 studies (75.0%) in the subregions of the hippocampus in patients with schizophrenia compared to that in controls, whereas the other two studies found no significant differences.
Published data have reported decreased subunit expression or receptor binding in the hippocampus in schizophrenia. These findings were inconsistent in other brain regions, which might be due to the heterogeneity of this population, various study design, physiological changes after death, and limited number of studies. Future in vivo studies are warranted to examine AMPA receptor expressions in human brains, together with their comprehensive clinical characterization.

Glyphosate-based herbicide has been the first choice for weed management worldwide since the 1970s, mainly due to its efficacy and reported low toxicity, which contributed to its high acceptance. Many of the recent studies focus solely on the persistence of pesticides in soils, air, water or food products, or even on the degree of exposure of animals, since their potential hazards to human health have raised concerns. Given the unaware exposure of the general population to pesticides, and the absence of a significant number of studies on occupational hazards, new glyphosate-induced toxicity data obtained for both residual and acute doses should be analyzed and systematized. Additionally, recent studies also highlight the persistence and toxicity of both glyphosate metabolites and surfactants present in herbicide formulations. To renew or ban the use of glyphosate, recently published studies must be taken into account, aiming to define new levels of safety for exposure to herbicide, its metabolites, and the toxic excipients of its formulations. This review aims to provide an overview of recent publications (2010-present) on in vitro and in vivo studies aimed at verifying the animal toxicity induced by glyphosate, its metabolite aminomethylphosphonic acid (AMPA) and glyphosate-based formulations, evaluated in various experimental models. Apart from glyphosate-induced toxicity, recent data concerning the role of surfactants in the toxicity of glyphosate-based formulations are discussed.

Glyphosate, a commonly used pesticide, has been the topic of much debate. The effects of exposure to glyphosate remains a contentious topic. This paper provides an update to the existing literature regarding levels of glyphosate exposure in occupationally exposed individuals and focuses or reviewing all the available published literature regarding glyphosate exposure levels in children.
A literature review was conducted and any articles reporting quantifiable exposure levels in humans published since January 2019 (the last published review on glyphosate exposure) were reviewed and data extracted and standardized.
A total of five new studies reporting exposure levels in humans were found including 578 subjects. Two of these studies focused on occupationally exposed individuals while three of them focused on glyphosate exposure levels in children. Given the sparse nature of the new data, previously identified studies on exposure to glyphosate in children were included in our analysis of children\'s exposure. The lowest average level of glyphosate exposure reported was 0.28 μg/L and the highest average exposure levels reported was 4.04 μg/L.
The literature on glyphosate exposure levels, especially in children, remains limited. Without more data collected in a standardized way, parsing out the potential relationship between glyphosate exposure and disease will not be possible.

Synaptic transmission is the basic mechanism of information transfer between neurons not only in the brain, but along all the nervous system. In this review we will briefly summarize some of the main parameters that produce stochastic variability in the synaptic response. This variability produces different effects on important brain phenomena, like learning and memory, and, alterations of its basic factors can cause brain malfunctioning.

The EFSA received from the European Commission a mandate to revise its previous review of the existing maximum residue levels (MRLs) for glyphosate taking into account additional data that were erroneously omitted in the evaluation report supporting the original MRL review. These additional data were evaluated by the Rapporteur Member State (RMS), Germany, and made available to EFSA in an addendum. Based on the assessment of the overall data available, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. The consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance glyphosate. To assess the occurrence of glyphosate residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived under Commission Regulation (EU) No 1141/2010 as amended by Commission Implementing Regulation (EU) No 380/2013, the MRLs established by the Codex Alimentarius Commission as well as the import tolerances and European authorisations reported by Member States (including the supporting residues data). Based on the assessment of the available data, MRL proposals were derived and a consumer risk assessment was carried out. Although no apparent risk to consumers was identified, some information required by the regulatory framework was missing. Hence, the consumer risk assessment is considered indicative only and some MRL proposals derived by EFSA still require further consideration by risk managers.

Glyphosate (Gly) is a broad-spectrum herbicide and currently one of the most studied pesticides. New Gly-related data are published daily worldwide. Despite the large number of publications, there is no published scientometric revision that presently addresses this issue systematically. We aimed to scientometrically analyze the publication patterns of main topics related to Gly research. Web of Science data was obtained searching the topic \"Glyphosate\" (10,069 publications). Toxicology was the most influential area, and a subset was delimited containing the categories \"Environmental Sciences\", \"Toxicology\" and \"Ecology\" (2077 publications). The datasets were analyzed using Citespace. The publications number presented a high correlation with the Gross Domestic Product (GDP) in both datasets. USA was the leader of general publication about Gly, followed by Brazil, Canada and China. USA, Canada, Argentina, China and Brazil were the main countries in Gly toxicology. This subset was related with data of the GDP spending on Research & Developing and with the number of researchers by country. Thus, we ranked the main countries interested in the Gly and its toxicology and that invest their economic and human resources in these researches. Based on a keyword analysis by CiteSpace of the Gly toxicology, it was highlighted the \"glyphosate-induced habitat alteration\", that reflected the concern about Gly impact on agricultural and natural ecosystems. The researchers are also focused in studies involving AMPA (aminomethylphosphonic acid), the main Gly degradation product, the genotoxicity, herbicides mixture and in its presence in drinking water. More researches about Gly genotoxicity and carcinogenicity to humans are needed and more studies to compile the results of independent researches, such as meta-analytical reviews. Our study can support decisions and future efforts about Gly impacts and use, since more sustainable agriculture with less environment impact is important to the maintenance of ecosystem services and consequently the human health.

It is widely accepted that glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures. Among glutamate receptors, the roles of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in physiological and pathological conditions represent major clinical research targets. It is well known that agonists of NMDA or AMPA receptors can elicit seizures in animal or human subjects, while antagonists have been shown to inhibit seizures in animal models, suggesting a potential role for NMDA and AMPA receptor antagonists in anti-seizure drug development. Several such drugs have been evaluated in clinical studies; however, the majority, mainly NMDA-receptor antagonists, failed to demonstrate adequate efficacy and safety for therapeutic use, and only an AMPA-receptor antagonist, perampanel, has been approved for the treatment of some forms of epilepsy. These results suggest that a misunderstanding of the role of each glutamate receptor in the ictogenic process may underlie the failure of these drugs to demonstrate clinical efficacy and safety. Accumulating knowledge of both NMDA and AMPA receptors, including pathological gene mutations, roles in autoimmune epilepsy, and evidence from drug-discovery research and pharmacological studies, may provide valuable information enabling the roles of both receptors in ictogenesis to be reconsidered. This review aimed to integrate information from several studies in order to further elucidate the specific roles of NMDA and AMPA receptors in epilepsy.