Tag: 400-500

On August 15, 2017, Platania, Chiara Bianca Maria; Giurdanella, Giovanni; Di Paola, Luisa; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio published an article.COA of Formula: C28H32N4O2S The title of the article was P2X7 receptor antagonism: Implications in diabetic retinopathy. And the article contained the following:

Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacol. target in DR. Here the authors first carried out an in silico mol. modeling study in order to characterize the allosteric pocket in P2X7R, and identify a suitable P2X7R antagonist through mol. docking. JNJ47965567 was identified as the hit compound in docking calculations, as well as for its absorption, distribution, metabolism and excretion (ADME) profile. As an in vitro model of early diabetic retinopathy, human retinal pericytes were exposed to high glucose (25 mM, 48 h) that caused a significant (p < 0.05) release of IL-1尾 and LDH. The block of P2X7R by JNJ47965567 significantly (p < 0.05) reverted the damage elicited by high glucose, detected as IL-1尾 and LDH release. Overall, the findings suggest that the P2X7R represents an attractive pharmacol. target to manage the early phase of diabetic retinopathy, and the compound JNJ47965567 is a good template to discover other P2X7R selective antagonists. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).COA of Formula: C28H32N4O2S

The Article related to p2x7 receptor antagonism diabetic retinopathy, diabetic retinopathy, il-1尾, inflammation, molecular modeling, p2x7 receptor, pericytes, Pharmacology: Effects Of Agents For Treating Metabolic and Endocrine Disorders and other aspects.COA of Formula: C28H32N4O2S

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Pasqualetto, Gaia; Brancale, Andrea; Young, Mark T. published an article in 2018, the title of the article was The molecular determinants of small-molecule ligand binding at P2X receptors.Synthetic Route of 1428327-31-4 And the article contains the following content:

P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiol. ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo- state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homol. modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators. P2X receptors are attractive drug targets, and a wide array of potent, subtype-selective modulators (mostly antagonists) have been developed. In 2016, crystal structures of human P2X3 in complex with the competitive antagonists TNP-ATP and A-317491, and Ailuropoda melanoleuca P2X7 in complex with a series of allosteric antagonists were published, giving fascinating insights into the mechanism of channel antagonism. In this article we not only summarize current understanding of small-mol. modulator binding at P2X receptors, but also use this information in combination with previously published structure-function data and mol. docking experiments, to hypothesize a role for the dorsal fin loop region in differential ATP potency, and describe novel, testable binding conformations for both the semi-selective synthetic P2X7 agonist 2′-(3′)-O-(4-benzoyl)benzoyl ATP (BzATP), and the P2X4-selective pos. allosteric modulator ivermectin. We find that the distal benzoyl group of BzATP lies in close proximity to Lys-127, a residue previously implicated in BzATP binding to P2X7, potentially explaining the increased potency of BzATP at rat P2X7 receptors. We also present mol. docking of ivermectin to rat P2X4 receptors, illustrating a plausible binding conformation between the first and second transmembrane domains which not only tallies with previous mutagenesis studies, but would also likely have the effect of stabilizing the open channel structure, consistent with the mode of action of this pos. allosteric modulator. From our docking simulations and anal. of sequence homol. we propose a series of mutations likely to confer ivermectin sensitivity to human P2X1. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Synthetic Route of 1428327-31-4

The Article related to mol determinants small mol ligand binding receptor, p2x, ion channel, ligand binding, molecular modeling, structure-function, Pharmacology: Effects Of Inflammation Inhibitors and Immune Agents and other aspects.Synthetic Route of 1428327-31-4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

On November 20, 2021, Garrosa-Jimenez, Javier; Sanchez Carro, Yolanda; Ovejero-Benito, Maria C.; del Sastre, Eric; Garcia, Antonio G.; Lopez, Manuela G.; Lopez-Garcia, Pilar; Cano-Abad, Maria F. published an article.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide The title of the article was Intracellular calcium and inflammatory markers, mediated by purinergic stimulation, are differentially regulated in monocytes of patients with major depressive disorder. And the article contained the following:

The P2X7 receptor (P2X7R) is a ligand-gated ion channel that is being recognized as a major player in neuropsychiatric disorders such as Major Depressive Disorder (MDD). P2X7R activation is triggered by high extracellular ATP concentrations, leading to channel opening and inducing an increase in cytosolic calcium concentration ([Ca2+]c), that activates the inflammatory pathway. Those receptors are expressed not only in CNS cells but also in peripheral blood cells, where they are activated in response to inflammatory mols. such as bacterial lipopolysaccharide (LPS). LPS induced-tissue damage promotes an elevation of extracellular ATP, triggering the NRLP3-inflammasome assembly and activation that, sequentially, induces caspase-1 cleavage and IL-1尾 processing and secretion. In this context, we attempt to understand the role of P2X7R in [Ca2+]c homeostasis regulation, inflammasome expression and its pharmacol. modulation in MDD. For this purpose, monocytes were isolated from peripheral blood of MDD patients and [Ca2+]c was monitored with the intracellular probe Fura-2. Our results point out to P2X7R as the responsible of the Ca2+ imbalance, as well as TNF-伪-dependent activation of caspase-1 in MDD patients. In addition, P2X7R blockade with its specific antagonist, JNJ-47965567, reduces the Ca2+ entry upon Bz-ATP exposure. Altogether, our results point that MDD patients have both, Ca2+ homeostasis alteration and an inflammatory status, which promote an independent-inflammasome activation of caspase-1. Therefore, we propose the pharmacol. modulation of P2X7R as a therapeutic approach against MDD symptoms. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

The Article related to human mdd calcium inflammatory marker purinergic stimulation monocyte, calcium homeostasis, inflammation, major depression disorder, p2x7 receptors, Mammalian Pathological Biochemistry: Nervous System and Psychiatric Diseases and other aspects.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Zhao, Ya-Fei; Ren, Wen-Jing; Zhang, Ying; He, Jin-Rong; Yin, Hai-Yan; Liao, Yang; Rubini, Patrizia; Deussing, Jan M.; Verkhratsky, Alexei; Yuan, Zeng-Qiang; Illes, Peter; Tang, Yong published an article in 2022, the title of the article was High, in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic, in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus.Electric Literature of 1428327-31-4 And the article contains the following content:

Extracellular ATP (ATP) in the brain is suggested to be an etiol. factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochem., and patch-clamp electrophysiol. in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacol. agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the resp. receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochem. demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacol. damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiol. of MDD in humans. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Electric Literature of 1428327-31-4

The Article related to acute stress depression astrocyte microglia receptor rodent hippocampus, p2x7 receptor, extracellular atp, hippocampus, major depression, mouse, rat, Mammalian Pathological Biochemistry: Nervous System and Psychiatric Diseases and other aspects.Electric Literature of 1428327-31-4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

On August 15, 2017, Platania, Chiara Bianca Maria; Giurdanella, Giovanni; Di Paola, Luisa; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio published an article.COA of Formula: C28H32N4O2S The title of the article was P2X7 receptor antagonism: Implications in diabetic retinopathy. And the article contained the following:

Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacol. target in DR. Here the authors first carried out an in silico mol. modeling study in order to characterize the allosteric pocket in P2X7R, and identify a suitable P2X7R antagonist through mol. docking. JNJ47965567 was identified as the hit compound in docking calculations, as well as for its absorption, distribution, metabolism and excretion (ADME) profile. As an in vitro model of early diabetic retinopathy, human retinal pericytes were exposed to high glucose (25 mM, 48 h) that caused a significant (p < 0.05) release of IL-1尾 and LDH. The block of P2X7R by JNJ47965567 significantly (p < 0.05) reverted the damage elicited by high glucose, detected as IL-1尾 and LDH release. Overall, the findings suggest that the P2X7R represents an attractive pharmacol. target to manage the early phase of diabetic retinopathy, and the compound JNJ47965567 is a good template to discover other P2X7R selective antagonists. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).COA of Formula: C28H32N4O2S

The Article related to p2x7 receptor antagonism diabetic retinopathy, diabetic retinopathy, il-1尾, inflammation, molecular modeling, p2x7 receptor, pericytes, Pharmacology: Effects Of Agents For Treating Metabolic and Endocrine Disorders and other aspects.COA of Formula: C28H32N4O2S

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Pasqualetto, Gaia; Brancale, Andrea; Young, Mark T. published an article in 2018, the title of the article was The molecular determinants of small-molecule ligand binding at P2X receptors.Synthetic Route of 1428327-31-4 And the article contains the following content:

P2X receptors are trimeric eukaryotic ATP-gated cation channels. Extracellular ATP-their physiol. ligand-is released as a neurotransmitter and in conditions of cell damage such as inflammation, and substantial evidence implicates P2X receptors in diseases including neuropathic pain, cancer, and arthritis. In 2009, the first P2X crystal structure, Danio rerio P2X4 in the apo- state, was published, and this was followed in 2012 by the ATP-bound structure. These structures transformed our understanding of the conformational changes induced by ATP binding and the mechanism of ligand specificity, and enabled homol. modeling of mammalian P2X receptors for ligand docking and rational design of receptor modulators. P2X receptors are attractive drug targets, and a wide array of potent, subtype-selective modulators (mostly antagonists) have been developed. In 2016, crystal structures of human P2X3 in complex with the competitive antagonists TNP-ATP and A-317491, and Ailuropoda melanoleuca P2X7 in complex with a series of allosteric antagonists were published, giving fascinating insights into the mechanism of channel antagonism. In this article we not only summarize current understanding of small-mol. modulator binding at P2X receptors, but also use this information in combination with previously published structure-function data and mol. docking experiments, to hypothesize a role for the dorsal fin loop region in differential ATP potency, and describe novel, testable binding conformations for both the semi-selective synthetic P2X7 agonist 2′-(3′)-O-(4-benzoyl)benzoyl ATP (BzATP), and the P2X4-selective pos. allosteric modulator ivermectin. We find that the distal benzoyl group of BzATP lies in close proximity to Lys-127, a residue previously implicated in BzATP binding to P2X7, potentially explaining the increased potency of BzATP at rat P2X7 receptors. We also present mol. docking of ivermectin to rat P2X4 receptors, illustrating a plausible binding conformation between the first and second transmembrane domains which not only tallies with previous mutagenesis studies, but would also likely have the effect of stabilizing the open channel structure, consistent with the mode of action of this pos. allosteric modulator. From our docking simulations and anal. of sequence homol. we propose a series of mutations likely to confer ivermectin sensitivity to human P2X1. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Synthetic Route of 1428327-31-4

The Article related to mol determinants small mol ligand binding receptor, p2x, ion channel, ligand binding, molecular modeling, structure-function, Pharmacology: Effects Of Inflammation Inhibitors and Immune Agents and other aspects.Synthetic Route of 1428327-31-4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

On November 20, 2021, Garrosa-Jimenez, Javier; Sanchez Carro, Yolanda; Ovejero-Benito, Maria C.; del Sastre, Eric; Garcia, Antonio G.; Lopez, Manuela G.; Lopez-Garcia, Pilar; Cano-Abad, Maria F. published an article.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide The title of the article was Intracellular calcium and inflammatory markers, mediated by purinergic stimulation, are differentially regulated in monocytes of patients with major depressive disorder. And the article contained the following:

The P2X7 receptor (P2X7R) is a ligand-gated ion channel that is being recognized as a major player in neuropsychiatric disorders such as Major Depressive Disorder (MDD). P2X7R activation is triggered by high extracellular ATP concentrations, leading to channel opening and inducing an increase in cytosolic calcium concentration ([Ca2+]c), that activates the inflammatory pathway. Those receptors are expressed not only in CNS cells but also in peripheral blood cells, where they are activated in response to inflammatory mols. such as bacterial lipopolysaccharide (LPS). LPS induced-tissue damage promotes an elevation of extracellular ATP, triggering the NRLP3-inflammasome assembly and activation that, sequentially, induces caspase-1 cleavage and IL-1β processing and secretion. In this context, we attempt to understand the role of P2X7R in [Ca2+]c homeostasis regulation, inflammasome expression and its pharmacol. modulation in MDD. For this purpose, monocytes were isolated from peripheral blood of MDD patients and [Ca2+]c was monitored with the intracellular probe Fura-2. Our results point out to P2X7R as the responsible of the Ca2+ imbalance, as well as TNF-α-dependent activation of caspase-1 in MDD patients. In addition, P2X7R blockade with its specific antagonist, JNJ-47965567, reduces the Ca2+ entry upon Bz-ATP exposure. Altogether, our results point that MDD patients have both, Ca2+ homeostasis alteration and an inflammatory status, which promote an independent-inflammasome activation of caspase-1. Therefore, we propose the pharmacol. modulation of P2X7R as a therapeutic approach against MDD symptoms. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

The Article related to human mdd calcium inflammatory marker purinergic stimulation monocyte, calcium homeostasis, inflammation, major depression disorder, p2x7 receptors, Mammalian Pathological Biochemistry: Nervous System and Psychiatric Diseases and other aspects.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Zhao, Ya-Fei; Ren, Wen-Jing; Zhang, Ying; He, Jin-Rong; Yin, Hai-Yan; Liao, Yang; Rubini, Patrizia; Deussing, Jan M.; Verkhratsky, Alexei; Yuan, Zeng-Qiang; Illes, Peter; Tang, Yong published an article in 2022, the title of the article was High, in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic, in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus.Electric Literature of 1428327-31-4 And the article contains the following content:

Extracellular ATP (ATP) in the brain is suggested to be an etiol. factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochem., and patch-clamp electrophysiol. in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacol. agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the resp. receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochem. demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacol. damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiol. of MDD in humans. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Electric Literature of 1428327-31-4

The Article related to acute stress depression astrocyte microglia receptor rodent hippocampus, p2x7 receptor, extracellular atp, hippocampus, major depression, mouse, rat, Mammalian Pathological Biochemistry: Nervous System and Psychiatric Diseases and other aspects.Electric Literature of 1428327-31-4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

On August 15, 2017, Platania, Chiara Bianca Maria; Giurdanella, Giovanni; Di Paola, Luisa; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore; Bucolo, Claudio published an article.COA of Formula: C28H32N4O2S The title of the article was P2X7 receptor antagonism: Implications in diabetic retinopathy. And the article contained the following:

Diabetic retinopathy (DR) is the most frequent complication of diabetes and one of leading causes of blindness worldwide. Early phases of DR are characterized by retinal pericyte loss mainly related to concurrent inflammatory process. Recently, an important link between P2X7 receptor (P2X7R) and inflammation has been demonstrated indicating this receptor as potential pharmacol. target in DR. Here the authors first carried out an in silico mol. modeling study in order to characterize the allosteric pocket in P2X7R, and identify a suitable P2X7R antagonist through mol. docking. JNJ47965567 was identified as the hit compound in docking calculations, as well as for its absorption, distribution, metabolism and excretion (ADME) profile. As an in vitro model of early diabetic retinopathy, human retinal pericytes were exposed to high glucose (25 mM, 48 h) that caused a significant (p < 0.05) release of IL-1β and LDH. The block of P2X7R by JNJ47965567 significantly (p < 0.05) reverted the damage elicited by high glucose, detected as IL-1β and LDH release. Overall, the findings suggest that the P2X7R represents an attractive pharmacol. target to manage the early phase of diabetic retinopathy, and the compound JNJ47965567 is a good template to discover other P2X7R selective antagonists. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).COA of Formula: C28H32N4O2S

The Article related to p2x7 receptor antagonism diabetic retinopathy, diabetic retinopathy, il-1β, inflammation, molecular modeling, p2x7 receptor, pericytes, Pharmacology: Effects Of Agents For Treating Metabolic and Endocrine Disorders and other aspects.COA of Formula: C28H32N4O2S

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Fischer, Wolfgang; Franke, Heike; Kruegel, Ute; Mueller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A.; Henshall, David C.; Engel, Tobias published an article in 2016, the title of the article was Critical evaluation of p2x7 receptor antagonists in selected seizure models.Electric Literature of 1428327-31-4 And the article contains the following content:

The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC- 5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chem.-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Electric Literature of 1428327-31-4

The Article related to seizure p2x7 receptor antagonist afc5128 jnj47965567, Pharmacology: Effects Of Nervous System- and Behavior-Affecting Drugs and Neuromuscular Agents and other aspects.Electric Literature of 1428327-31-4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics