Enhancing ultrafiltration performance for dairy wastewater treatment using a 3D printed turbulence promoter.

Dairy factories annually generate an increasing amount of wastewater, which can cause eutrophication due to high concentrations of amino acids and lipids. To address this issue, membrane technology has emerged as a promising solution, but membrane fouling remains a significant challenge, since it can cause decreased flux, decrease membrane rejection performance, and increased energy demand. This study aimed to reduce membrane fouling by integrated a three-dimensional printed (3DP) turbulence promoter into an ultrafiltration dead-end cell and varying stirring speeds. Two mathematical models, Hermia and resistance-in-series, were used to analyze the fouling process. According to both models, the cake layer formation model indicated the most prevalent fouling mechanism. Specific energy demand, permeate flux, membrane rejection, and membrane reversible and irreversible resistances were measured, calculated, and compared. The results suggest that the combination of an integrated 3DP turbulence promoter and high stirring speeds can effectively reduce membrane fouling in a dairy wastewater treatment module.

Evaluation of vibratory shear-enhanced processing module-integrated three-dimensional printed spacers for enhanced wastewater ultrafiltration.

The article evaluates the effectiveness of two new designed module-integrated three-dimensional (3D) printed spacers in enhancing wastewater ultrafiltration efficiencies using vibratory shear-enhanced processing (VSEP). The study investigates the star-shaped spacer filled module channel (star spacer) and the column-shaped herringbone spacer filled module channel with the same position as the flow direction (column spacer) and with the opposite position as the flow direction (rev column spacer). It compares the VSEP module-integrated spacers with membrane module vibration (module vibration) and empty membrane module channel (control) configurations. The results show that the module integration of the 3D printed spacers can greatly improve the specific, average, and constant permeate fluxes and can contribute to reducing the total, reversible and irreversible resistance values, and specific energy consumption of the ultrafiltration membrane separation experiments. Overall, this study provides valuable insights into improving the performance of wastewater ultrafiltration systems and fouling mitigation through the module integration of 3D printed spacers and membrane module vibration. PRACTITIONER POINTS: Vibratory shear-enhanced processing (VSEP) ultrafiltration module-integrated 3D printed spacers were successfully fabricated and evaluated for improved wastewater treatment. Two spacer designs, a star-shaped and a column-shaped herringbone, were compared with an empty membrane module channel with and without vibration. Two configurations of the column-shaped spacer, in the same and reversed flow direction, were tested. Specific energy consumption was calculated and compared for all configurations. Significant improvements in ultrafiltration performance were observed with the use of spacers compared with an empty module channel, including enhanced permeate fluxes and reductions in both total and reversible, as well as irreversible, resistance.

Investigation of Different Pre-Treatment Techniques and 3D Printed Turbulence Promoter to Mitigate Membrane Fouling in Dairy Wastewater Module.

This study investigates the enhancement of dairy wastewater treatment using chemical and physical pre-treatments coupled with membrane separation techniques to reduce membrane fouling. Two mathematical models, namely the Hermia and resistance-in-series module, were utilized to comprehend the mechanisms of ultrafiltration (UF) membrane fouling. The predominant fouling mechanism was identified by fitting experimental data into four models. The study calculated and compared permeate flux, membrane rejection, and membrane reversible and irreversible resistance values. The gas formation was also evaluated as a post-treatment. The results showed that the pre-treatments improved UF efficiency for flux, retention, and resistance values compared to the control. Chemical pre-treatment was identified as the most effective approach to improve filtration efficiency. Physical treatments after microfiltration (MF) and UF showed better fluxes, retention, and resistance results than ultrasonic pre-treatment followed by UF. The efficacy of a three-dimensionally printed (3DP) turbulence promoter was also examined to mitigate membrane fouling. The integration of the 3DP turbulence promoter enhanced hydrodynamic conditions and increased the shear rate on the membrane surface, shortening filtration time and increasing permeate flux values. This study provides valuable insights into optimizing dairy wastewater treatment and membrane separation techniques, which can have significant implications for sustainable water resource management. The present outcomes clearly recommend the application of hybrid pre-, main- and post-treatments coupled with module-integrated turbulence promoters in dairy wastewater ultrafiltration membrane modules to increase membrane separation efficiencies.

Modeling of Organic Fouling in an Ultrafiltration Cell Using Different Three-Dimensional Printed Turbulence Promoters.

Designing turbulence promoters with optimal geometry and using them for ultrafiltration systems has been a key challenge in mitigating membrane fouling. In this study, six different turbulence promoters were created using three-dimensional printing technology and applied in dead-end ultrafiltration. Three-dimensional-printed (3DP) turbulence promoter configurations were integrated into a classical batch ultrafiltration cell. The effects of these configurations and the stirring speeds on the permeate filtration flux, organic rejections, and membrane resistances were investigated. The fouling control efficiency of the 3DP promoters was evaluated using two polyethersulfone membranes in a stirred ultrafiltration cell with model dairy wastewater. The Hermia and resistance-in-series models were studied to further investigate the membrane fouling mechanism. Of the Hermia models, the cake layer model best described the fouling in this membrane filtration system. It can be concluded that the 3DP turbulence promoters, combined with intense mechanical stirring, show great promise in terms of permeate flux enhancement and membrane fouling mitigation. Using a well-designed 3DP turbulence promoter improves the hydrodynamic flow conditions on the surface of the stirred membrane separation cells based on computational fluid dynamics modeling. Therefore, the factors effecting the fabrication of 3DP turbulence promoters are important, and further research should be devoted to revealing them.

Surface-initiated polymerization of PVDF membrane using amine and bismuth tungstate (BWO) modified MIL-100(Fe) nanofillers for pesticide photodegradation.

Pirimicarb as a pesticide is used to control the aphids in the agriculture field; however, it affects the groundwater ecosystem by leaching through the soil profile. The post-synthetic amine and BWO modified MIL-100 (Fe) nanofillers were synthesized. The photocatalytic property of amine-functionalized and BWO@MIL-100(Fe) nanofillers was confirmed by the lesser bandgap energy than the unmodified MIL-100 (Fe) nanofiller. Herein, we constructed a nanofillers grafted PVDF membrane via in-situ polymerization technique for the pirimicarb reduction and photodegradation. Furthermore, the nanofiller's grafted membranes were characterized by FESEM, XRD, FTIR, and contact angle analysis. The carboxylic acid peak was observed on the FTIR which demonstrated the PAA grafted on the membrane surface and similar crystalline peaks evident that the nanofillers were grafted on the membrane surface. Furthermore, surface morphology studies have exhibited the dispersion of nanofillers and enhanced microvoids in the cross-section of the membrane. The decrease in the water contact angle of the membrane depicted the improved antifouling properties and surface energy. The nanofiller's grafted membranes have shown higher hydrophilicity correlated well with the enhanced pure water flux in the order M4 > M5 > M2 > M3 > M6 > M7 compared to the neat membrane (M1). In BWO@MIL-100(Fe) membrane has shown a higher permeate flux (25.99 L m-2.h-1) than the neat PVDF membrane. The BWO@MIL-100(Fe) grafted PVDF membrane has also shown excellent pirimicarb photodegradation of 81% at pH 5. The proposed MIL-100 (Fe) and bismuth tungsten nanocomposite will pave the way for the different MOF-based photocatalytic materials for membrane-based pesticide degradation.

Comparison of filtering models for milk substitutes.

Membrane-based methods of filtering are becoming increasingly popular in the food industry, but membrane fouling significantly affects filtration performance, making the characterisation of fouling mechanisms critical. This study examined the applicability of three mathematical models. The resistance-in-series model divides the total resistance into membrane resistance, reversible resistance and irreversible resistance. The Hermia models distinguish four basic blocking mechanisms, namely complete blocking, standard blocking, intermediate blocking and cake filtration. The Makardij model analyses the flux-reducing or -enhancing effects. In the experiments, different models were investigated and compared. The feed solution was two milk substitute drinks (soy and oat) that were ultrafiltered under different operating parameters (transmembrane pressures: 0.05-0.1 MPa, stirring rate: 100-400 min-1). By fitting the data to the models, the most characteristic blocking mechanism and the rate constant that most influenced flux could be determined.

Recent development of photocatalytic nanomaterials in mixed matrix membrane for emerging pollutants and fouling control, membrane cleaning process.

Membrane-based separation is an area of extensive research in wastewater treatment, which includes the control of pollution and reuse of water. The fabrication and modification membranes for prevention and reduction of pollution to provide quality water with fouling-free membranes through the wastewater treatment are the progressive approaches in the industries. Several research works have been extensively working on modification and fabrication polymer membranes with integration of advanced oxidation process (AOP) to overcome the membrane fouling. This review describes the modification of membranes with various nanomaterials such as inorganic and modified carbon which can be used for pollution control and enhance the anti-fouling properties of ultrafiltration membranes. The effects on nanomaterials loading percentage, nanomaterials interaction with the polymers and rejection performances of the surface tuned membrane are elaborated. Secondly, the fouled membrane chemical cleaning process and NaOCl adverse effect on polymer structure are critically investigated. Moreover, state-of-art in the photocatalytic self-cleaning process are reviewed in this manuscript, and future perspectives on fouling mitigation based on AOP integrated membrane technology have also discussed.

Matrix effect in case of purification of oily waters by membrane separation combined with pre-ozonation.

In the present study, oil in water emulsions (coil = 100 ppm; doil droplets < 2 µm) was purified with ozonation followed by microfiltration using polyethersulfone (PES) membrane (dpore = 0.2 µm). The effects of pre-ozonation on membrane microfiltration were investigated in detail both in case of ultrapure and model groundwater matrices, applying different durations (0, 5, 10, and 20 min) of pre-ozonation. Simultaneously, the effects of added inorganic water components on the combined method were investigated. Size distribution of oil droplets, zeta potentials, fluxes, and purification efficiencies were measured and fouling mechanisms were described in all cases. It was found that the matrix significantly affected the size distribution and adherence ability of oil droplets onto the membrane surface, therefore fouling mechanisms also were strongly dependent on the matrix. In case of low salt concentration, the total resistance was caused mainly by reversible resistance, which could be significantly reduced (eliminated) by pre-ozonation. In case of model groundwater matrix, nearly twice higher total resistance was measured, and irreversible resistance was dominant, because of the higher adhesion ability of the oil droplets onto the membrane surface. In this case, pre-ozonation resulted in much lower irreversible, but higher reversible resistance. Increased duration of pre-ozonation raised the total resistance and reduced the elimination efficiency (due to fragmented oil droplets and water soluble oxidation by-products) in both cases, therefore short pre-ozonation can be recommended both from economic and performance aspects.

Fouling mitigation and cleanability of TiO2 photocatalyst-modified PVDF membranes during ultrafiltration of model oily wastewater with different salt contents.

In the present study, TiO2-coated ultrafiltration membranes were prepared and used for oily water filtration (droplet size < 2 µm). The aim of this work was to investigate the effect of different salt contents on fouling and filtration properties of neat and TiO2-coated membranes during oil-in-water emulsion filtration. The effect of the TiO2 coating on the flux, surface free energy, and retention values was measured and compared with the neat membrane values. The cleanability of the fouled TiO2-coated membranes by UV irradiation was also investigated by measuring flux recovery and contact angles, and the chemical changes during cleaning were characterized by ATR-IR. It was found that increasing the salt content of the model wastewaters, oil-in-water emulsions, increased the zeta potential and the size of the droplets. The presence of the TiO2 coating decreases the membrane fouling during oily emulsion filtration compared to the neat membrane, due to the hydrophilicity of the coating regardless of the salt content of the emulsions. The neat and coated membrane oil retention was similar, 96 ± 2%. The coated membrane can be effectively cleaned with UV irradiation without additional chemicals and a significant flux recovery can be achieved. Monitoring of the cleaning process by following the membrane surface wettability and ATR-IR measurements showed that the recovery of flux does not mean the total elimination of the oil layer from the membrane surface.

Selective inhibition of extra-synaptic α5-GABAA receptors by S44819, a new therapeutic agent.

In the mammalian central nervous system (CNS) GABAA receptors (GABAARs) mediate neuronal inhibition and are important therapeutic targets. GABAARs are composed of 5 subunits, drawn from 19 proteins, underpinning expression of 20-30 GABAAR subtypes. In the CNS these isoforms are heterogeneously expressed and exhibit distinct physiological and pharmacological properties. We report the discovery of S44819, a novel tricyclic oxazolo-2,3-benzodiazepine-derivative, that selectively inhibits α5-subunit-containing GABAARs (α5-GABAARs). Current α5-GABAAR inhibitors bind to the "benzodiazepine site". However, in HEK293 cells expressing recombinant α5-GABAARs, S44819 had no effect on 3H-flumazenil binding, but displaced the GABAAR agonist 3H-muscimol and competitively inhibited the GABA-induced responses. Importantly, we reveal that the α5-subunit selectivity is uniquely governed by amino acid residues within the α-subunit F-loop, a region associated with GABA binding. In mouse hippocampal CA1 neurons, S44819 enhanced long-term potentiation (LTP), blocked a tonic current mediated by extrasynaptic α5-GABAARs, but had no effect on synaptic GABAARs. In mouse thalamic neurons, S44819 had no effect on the tonic current mediated by δ-GABAARs, or on synaptic (α1ß2γ2) GABAARs. In rats, S44819 enhanced object recognition memory and reversed scopolamine-induced impairment of working memory in the eight-arm radial maze. In conclusion, S44819 is a first in class compound that uniquely acts as a potent, competitive, selective antagonist of recombinant and native α5-GABAARs. Consequently, S44819 enhances hippocampal synaptic plasticity and exhibits pro-cognitive efficacy. Given this profile, S44819 may improve cognitive function in neurodegenerative disorders and facilitate post-stroke recovery.

A novel GABA(A) alpha 5 receptor inhibitor with therapeutic potential.

Novel 2,3-benzodiazepine and related isoquinoline derivatives, substituted at position 1 with a 2-benzothiophenyl moiety, were synthesized to produce compounds that potently inhibited the action of GABA on heterologously expressed GABAA receptors containing the alpha 5 subunit (GABAA α5), with no apparent affinity for the benzodiazepine site. Substitutions of the benzothiophene moiety at position 4 led to compounds with drug-like properties that were putative inhibitors of extra-synaptic GABAA α5 receptors and had substantial blood-brain barrier permeability. Initial characterization in vivo showed that 8-methyl-5-[4-(trifluoromethyl)-1-benzothiophen-2-yl]-1,9-dihydro-2H-[1,3]oxazolo[4,5-h][2,3]benzodiazepin-2-one was devoid of sedative, pro-convulsive or motor side-effects, and enhanced the performance of rats in the object recognition test. In summary, we have discovered a first-in-class GABA-site inhibitor of extra-synaptic GABAA α5 receptors that has promising drug-like properties and warrants further development.

Egis-11150: a candidate antipsychotic compound with procognitive efficacy in rodents.

Classical antipsychotics, e.g. haloperidol, chlorpromazine, are potent at controlling the positive symptoms of schizophrenia but frequently elicit extrapyramidal motor side-effects. The introduction of atypical antipsychotics such as risperidone, olanzapine and clozapine has obviated this problem, but none of the current drugs seem to improve the cognitive deficits accompanying schizophrenia. Thus there is an unmet need for agents that not only suppress the psychotic symptoms but also ameliorate the impairment of cognition. Here, we report the preclinical properties of a candidate antipsychotic, Egis-11150, that shows marked pro-cognitive efficacy. Egis-11150 displayed high affinity for adrenergic α(1), α(2c), 5-HT(2A) 5-HT7, moderate affinity for adrenergic α(2a) and D2 receptors. It was a functional antagonist on all of the above receptors, with the exception of 5-HT7 receptors, where it was an inverse agonist. Phencyclidine-induced hypermotility in mice and inhibition of conditioned avoidance response in rats were assessed to estimate efficacy against the positive and social withdrawal test in rats was used to predict efficacy against the negative symptoms of schizophrenia. Passive-avoidance learning, novel object recognition and radial maze tests in rats were used to assess pro-cognitive activity, while phencyclidine-induced disruption of prepulse inhibition in mice was examined to test for effects on attention. Egis-11150 (0.01-0.3 mg/kg, ip.) was effective in all of the preclinical models of schizophrenia examined. Moreover, a robust pro-cognitive profile was apparent. In summary, work in preclinical models indicates that Egis-11150 is a potential treatment for controlling the psychosis as well as the cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Temporal alteration of spreading depression by the glycine transporter type-1 inhibitors NFPS and Org-24461 in chicken retina.

We used isolated chicken retina to induce spreading depression by the glutamate receptor agonist N-methyl-d-aspartate. The N-methyl-d-aspartate-induced latency time of spreading depression was extended by the glycine(B) binding site competitive antagonist 7-chlorokynurenic acid. Addition of the glycine transporter type-1 inhibitors NFPS and Org-24461 reversed the inhibitory effect of 7-chlorokynurenic acid on N-methyl-d-aspartate-evoked spreading depression. The glycine uptake inhibitory activity of Org-24461, NFPS, and some newly synthesized analogs of NFPS was determined in CHO cells stably expressing human glycine transporter type-1b isoform. Compounds, which failed to inhibit glycine transporter type-1, also did not have effect on retinal spreading depression. These experiments indicate that the spreading depression model in chicken retina is a useful in vitro test to determine activity of glycine transporter type-1 inhibitors. In addition, our data serve further evidence for the role of glycine transporter type-1 in retinal neurotransmission and light processing.

Deramciclane improves object recognition in rats: potential role of NMDA receptors.

The cognition-enhancing properties of deramciclane (N,N-dimethyl-2-([(1R,4R,6S)-1,7,7-trimethyl-6-phenyl-6-bicyclo[2.2.1]heptanyl]oxy)ethanamine) and memantine (3,5-dimethyl-tricyclo[3.3.1.1(3,7)]decylamine-3,5-dimethyladamantan-1-amine) were evaluated in the novel object recognition (OR) test in the rat, while their effect in comparison with other N-methyl-D-aspartate (NMDA) receptor blockers such us MK-801 ([+]-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) and CPP ([+/-]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) on NMDA-evoked spreading depression (SD) was investigated in the chicken retina, in vitro. In the OR test, pretreatment of rats with either deramciclane (30 mg/kg p.o.) or memantine (10 and 30 mg/kg, p.o.) resulted in preference for the novel object, compared to the familiar one, indicating procognitive activity of the compounds. In the in vitro studies memantine (10-30 M), or deramciclane (30-100 M) as well as CPP (0.1-1 M), MK-801 (0.3-1 M), concentration-dependently inhibited NMDA evoked SD. Furthermore, the inhibitory effect of memantine, deramciclane and MK-801 was activity-dependent. These results support the role of NMDA receptors in the procognitive effect of deramciclane.

2,3-benzodiazepine-type AMPA receptor antagonists and their neuroprotective effects.

AMPA receptors are fast ligand-gated members of glutamate receptors in neuronal and many types of non-neuronal cells. The heterotetramer complexes are assembled from four subunits (GluR1-4) in region-, development- and function-selective patterns. Each subunit contains three extracellular domains (a large amino terminal domain, an agonist-binding domain and a transducer domain), and three transmembrane segments with a loop (pore forming domain), as well as the intracellular carboxy terminal tail (traffic and conductance regulatory domain). The binding of the agonist (excitatory amino acids and their derivatives) initiates conformational realignments, which transmit to the transducer domain and membrane spanning segments to gate the channel permeable to Na+, K+ and more or less to Ca2+. Several 2,3-benzodiazepines act as non-competitive antagonists of the AMPA receptor (termed also negative allosteric modulators), which are thought to bind to the transducer domains and inhibit channel gating. Analysing their effects in vitro, it has been possible to recognize a structure-activity relationship, and to describe the critical parts of the molecules involved in their action at AMPA receptors. Blockade of AMPA receptors can protect the brain from apoptotic and necrotic cell death by preventing neuronal excitotoxicity during pathophysiological activation of glutamatergic neurons. Animal experiments provided evidence for the potential usefulness of non-competitive AMPA antagonists in the treatment of human ischemic and neurodegenerative disorders including stroke, multiple sclerosis, Parkinson's disease, periventricular leukomalacia and motoneuron disease. 2,3-benzodiazepine AMPA antagonists can protect against seizures, decrease levodopa-induced dyskinesia in animal models of Parkinson's disease demonstrating their utility for the treatment of a variety of CNS disorders.

The effects of AMPA receptor antagonists in models of stroke and neurodegeneration.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists have been shown to have neuroprotective effects in stroke models and although clinical trials with some agents are still ongoing, published results have not been favourable. We therefore wished to compare the effects of GYKI 52466, GYKI 53405, EGIS-8332 and EGIS-10608, non-competitive AMPA receptor antagonists with homophthalazine chemical structures, in standard animal stroke models with effects in a neurodegenerative model--excitoxicity in newborn mice. All compounds inhibited the S-AMPA-induced spreading depression in the chicken retina, in vitro, and were potent anticonvulsants against maximal electroshock in mice, in vivo. The AMPA receptor antagonists prevented domoate-induced cell death of motoneurons, in vitro, and reduced infarct size in a dose-dependent manner in the permanent middle cerebral artery occlusion model in mice, in vivo. In newborn mice (P5, histopathology at P10), local injection of the AMPA receptor agonist S-bromo-willardiine at day 5 after birth induced cortical damage and white matter damage, which was reduced in a dose-dependent manner by the AMPA receptor antagonists. EGIS 10608 was a very powerful receptor antagonist of white matter damage. In contrast, GYKI 52466 did not antagonize cortical and white matter damage induced by ibotenic acid. These models allow quantification of the effects of AMPA receptor antagonists in vitro and in vivo.

Interactions of allosteric modulators of AMPA/kainate receptors on spreading depression in the chicken retina.

The functional role of AMPA and kainate receptors in spreading depression (SD) was investigated in the isolated chicken retina. Competitive (NBQX) and non-competitive (GYKI 52466, GYKI 53405 and GYKI 53655) antagonists of the AMPA receptor inhibited AMPA-induced SD in a concentration-dependent manner. Concentrations of drugs caused 50% inhibition (IC(50) values) are 0.2, 16.6, 7.0 and 1.4 microM, respectively. AMPA receptor positive modulator cyclothiazide was more effective in the potentiation of SD evoked by AMPA than by kainate. Slight potentiation of either AMPA- or kainate-induced SD was observed only at high concentration (1 mg/ml) by the kainate receptor modulator concanavalin A. Compounds that positively modulate AMPA receptor function (cyclothiazide, IDRA-21, S 18986, 1-BCP and aniracetam) caused a concentration-dependent potentiation in SD. Concentrations of drugs that caused 50% potentiation (estimated EC(50) values) are 9, 135, 142, 450 and 1383 microM, respectively. Interaction between cyclothiazide, aniracetam or S 18986 administered with each other, or with GYKI 52466, respectively, was also investigated. When cyclothiazide and S 18986 were co-applied, their effects seemed to be additive. However, lack of additivity was obtained when S 18986 was added together with aniracetam. Positive modulators applied at equiactive concentrations reduced the inhibitory action of GYKI 52466 and differently shifted its concentration-response curve. In this respect, S 18986 was the most effective (IC(50) of GYKI 52466 changed from 16.6 to 51.9 microM). Our findings indicate the contribution of AMPA rather than kainate receptors in the mediation of retinal spreading depression. Our data further support the idea that multiple positive modulatory sites are present on the AMPA receptor complex in addition to a negative modulatory site.

Comparison of the AMPA antagonist action of new 2,3-benzodiazepines in vitro and their neuroprotective effects in vivo.

PURPOSE: AMPA receptor-mediated excitotoxicity is thought to be a critical process in diseases accompanied by neuronal cell loss following a hypoxic/anoxic state of the central nervous system. It has been suggested that blockade of AMPA receptors might result in significant protection of neurons against cellular damage. For testing the hypothesis, in vitro efficacy and in vivo neuroprotective action of new 2,3-benzodiazepine (2,3BDZ) AMPA antagonists have been compared. METHODS: 2.3BDZs were tested on kainate-evoked whole-cell currents in cultured neurons as well as on population spikes (PS) in rat hippocampal slices. Data were correlated with those obtained from the spreading depression (SD) experiments in chicken retina. Compounds were also examined in the gerbil bilateral carotid occlusion model (BCO), where percentage decrease of ischemia-related hypermotility (HM), impaired spatial memory (SA), and hypoxia-induced hippocampal CA1 neuronal cell death (CA1) were evaluated. RESULTS: Certain structural modifications of classical 2,3BDZs resulted in increased in vitro activity and improved in vivo efficacy. In particular, the halogen-substituted compounds EGIS-9879 and EGIS-9883 showed the highest neuroprotective efficacy (84% and 47% protection in CA1, 71% and 82% decrease in HM, respectively; 4 x 5 mg/kg i.p.) in BCO. PS and SD were correlated to the decrease of neuronal loss in the CA1 area. Lack of significant correlation was found between PS and CA1 (r = 0.437, p = 0.079) or SD and CA1 (r = 0.380, p = 0.146). CONCLUSIONS: Several new 2.3BDZ AMPA receptor antagonists have been synthesized at EGIS Pharmaceuticals characterized by remarkable in vitro and corresponding in vivo neuroprotective properties.