29 results about "AMPA receptor activity" patented technology

Provided is a polypeptide which contains a polypeptide having at least 80%, 85%, 90%, 95%, or 99% identity to amino acid sequence MTYRPGYNPFG (SEQ ID NO: 41) or amino acid sequence AKGYYRPYGVPV (SEQ ID NO: 22), or a polypeptide having one or more amino acid substitutions, deletions and / or additions relative to the amino acid sequence as shown in SEQ ID NO: 41 or 22. The provided polypeptide can interfere with the binding of a Brag2 synaptic protein to the C terminus of an AMPA receptor, thereby inhibiting NMDA-mediated excessive endocytosis of an AMPA receptor and neuronal apoptosis, and playing a role in protecting neuronal cell activity. Therefore, the polypeptide has application prospects and potential development values as a drug for treating nervous system diseases such as strokes, depression, Alzheimer's disease and drug addiction.

The application belongs to the technical field of biological medicine, and discloses a synthesis method of aryl F-18 labeled sulfuryl chloride and application of the aryl F-18 labeled sulfuryl chloride in amine compound labeling. The method takes thiophenol derivative as a labeling precursor, obtains F-18 labeled thiophenol intermediate through photocatalytic aryl F-18 fluorination reaction, and then obtains aryl F-18 labeled sulfuryl chloride through N-chlorosuccinimide oxidation chlorination. The obtained aryl F-18 labeled sulfuryl chloride (4-[ 18 F] fluorobenzenesulfonyl chloride) can occur sulfurylization reaction with various amine compounds at room temperature, and the radiochemical conversion rate is as high as 98%. The application is successfully applied to novel synthesis of AMPA receptor PET imaging agent[ 18 F]2 (the conversion rate is 96%, which is much higher than 13% reported in the literature). The application has the advantages of mild reaction condition, high conversion rate and wide substrate application range, and provides an efficient method for innovative preparation of F-18 labeled PET probes.

The present invention belongs to the field of medicinal chemistry technology, specifically relating to GluA2 AMPAR endocytosis-blocking transmembrane cyclic peptides and their applications. The present invention is based on the nine active amino acid sequence (GluA2-3Y) at the end of the AMPA receptor GluA2 subunit, undergoing structural modification and engineering. A hydrophobic group is attached to the N-terminus of the peptide, and amino acids at different positions in the peptide sequence are replaced with two cysteines according to a specific pattern. The sulfhydryl groups on the cysteines are then linked using a chemical linker to partially cyclicize the peptide sequence, thereby stabilizing the peptide sequence conformation, enhancing the transmembrane ability of the modified peptide, and improving the stability of the peptide sequence.

The invention relates to the field of bioengineering, in particular to application of GluA2 protein in an mPFC region as a target spot in preparation of a medicine for treating post-stroke depression. According to the application disclosed by the invention, by establishing a PSD model and detecting depression-like behaviors, the action and mechanism of the surface expression of an NSF protein S-nitrosation modification mediated GluA2-conforming AMPA receptor in the PSD are researched, the S-nitrosation level of NSF in an mPFC region and the interaction of GluA2-NSF are adjusted to be a target spot with clinical application potential for treating post-stroke depression, and the application has the advantages that the application range is wide, and the application prospect is wide. The method is beneficial for designing a medicine and a treatment method for treating post-stroke depression aiming at the NSF-GluA21, and has important scientific value and application prospect.

To provide a method and a computing device that allow for more effective determination regarding which patients will experience drug efficacy, and which patients will experience adverse drug events, and that provide personalized recommendations for patients regarding dose, the frequency of drug administration, and drug choice.SOLUTION: A method for identifying patients diagnosed with treatment resistant or refractory depression, pain or other clinical indications, who are eligible to receive N-methyl-D-aspartate receptor antagonist, glycine receptor beta modulator, or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-based therapies.SELECTED DRAWING: None

The present disclosure relates to oral compositions that include at least two agents selected from: agents that increase the concentration of glutamate; agents that increase dopamine production; agents that increase the concentration of brain-derived neurotrophic factor (BDNF); NMDA and / or AMPA receptor modulators; and acetylcholinesterase inhibitors. In son embodiments, a composition as provided herein includes D-glutamine present in an amount of about 20% to about 30% w / w of the composition; ginkgolide B present in an amount of about 0.1% to about 0.4% w / w of the composition; phosphatidylserine present in an amount of about 65% to about 80% w / w of the composition; and ascorbic acid present in an amount of about 0.5% to about 2.5% w / w of the composition. Such compositions are useful for improving memory and / or focus.

This invention relates to the use of (i) a 5-HT2A agonist (including 5-HT2A agonists that bind to a BDNF receptor, e.g., a 5-HT2A agonist that binds to the TrkB receptor or p75NTR), (ii) a therapeutic agent that promotes neuroplasticity by stimulation of the 5-HT2A receptor, (iii) a therapeutic agent that releases BDNF by stimulation of the 5-HT2A receptor (including those therapeutic agents that stimulate the 5-HT2A receptor and bind to a TrkB receptor or p75NTR), (iv) an AMPA positive allosteric modulator, (v) a therapeutic agent that promotes neuroplasticity by stimulation of the AMPA receptor, (vi) a therapeutic agent that releases BDNF by stimulation of the AMPA receptor, or (vii) an NMDA receptor positive allosteric modulator (such as a stinel compound) in the treatment of a psychiatric condition in which depressive symptoms are prominent, including major depressive disorder (MDD), bipolar disorder, post-traumatic stress disorder, substance use disorder, and depression-related aspects of schizophrenia (e.g. negative symptoms) in select patients who, for instance, have objectively determined cognitive impairment or poor cognition (such as objectively determined impaired learning and / or memory) and / or certain EEG characteristics.

The invention belongs to the technical field of biological medicine, and particularly relates to an anti-depression drug, a composite microsphere and a preparation method of the composite microsphere, and the anti-depression drug provided by the invention has excellent inhibitory activity on 5-HT reuptake and AMPA receptors and has an excellent treatment effect. In addition, the anti-depression drug microspheres provided by the invention are high in encapsulation efficiency, large in drug loading capacity, excellent in drug sustained release effect, better in human body absorption effect, capable of remarkably reducing the drug use frequency and / or the use dosage and small in toxic and side effects.

The invention provides compounds of the formula (I):wherein A1, A2, R2, R4, B1, B2, X, X1, n, a and b are as defined are defined in the specification, to pharmaceutical compositions comprising the compounds and the compounds for use as medicaments. The compounds potentiate AMPA receptor function and are expected to be useful in the treatment of central nervous system disorders, for example in the treatment of depressive disorders, mood disorders and cognitive dysfunction associated with neuropsychiatric disorders such as schizophrenia.

An aqueous pharmaceutical formulation of a solubilizing agent with a pyridone compound that is useful as an inhibitor to non-NMDA receptors, particularly to the AMPA receptor is disclosed herein. In some embodiments the pyridone compound is supersaturated in aqueous solution at pH between 6 and 8. The formulations are particularly useful as intravenous injections.

The present application provides compounds of Formula (I) and related compositions and methods, including methods of therapy for treating nervous system diseases and disorders, including multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), and methods for in vivo imaging of AMPA receptors or surrogates thereof in the brain. (I)

The invention relates to the field of biological medicines, in particular to a polypeptide, which comprises a polypeptide having at least 80%, 85%, 90%, 95% or 99% identity with an amino acid sequence MTYRPGYNPFG (SEQ ID NO: 41) or an amino acid sequence AKGYYRPYGVPV (SEQ ID NO: 22), or a polypeptide having one or more amino acid substitution, deletion and / or addition with the amino acid sequence shown as SEQ ID NO: 41 or 22. The polypeptide provided by the invention can be used for inhibiting NMDA-mediated AMPA receptor excessive endocytosis and neuronal apoptosis by interfering the mutual combination of the C terminal of the AMPA receptor and a Bragg 2 synaptic protein, so that the effect of protecting the activity of neuronal cells is achieved; therefore, the compound has an application prospect and a potential development value as a medicine for treating nervous system diseases such as cerebral apoplexy, depression, Alzheimer's disease, drug addiction and the like.

The invention provides compounds of the formula (I): (I) wherein A1, A2, R2, R4, B1, B2, X, X1, n, a and b are as defined are defined in the specification, to pharmaceutical compositions comprising the compounds and the compounds for use as medicaments. The compounds potentiate AMPA receptor function and are expected to be useful in the treatment of central nervous system disorders, for example in the treatment of depressive disorders, mood disorders and cognitive dysfunction associated with neuropsychiatric disorders such as schizophrenia.

The present disclosure provides, in part, a method of treating a disease, disorder, or condition mediated by AMPA receptor activity in a subject in need thereof, the method comprising orally administering a daily dose of Compound 1 or a pharmaceutically acceptable salt thereof to the subject, wherein the daily dose is from about 0.1 mg to about 5 mg of Compound 1 or a pharmaceutically acceptable salt thereof.

The present invention relates to pharmacogenomic decision support for modulators of NMDA, glycine and AMPA receptors. Used for identifying diagnosed as having therapeutically resistant or refractory depression, pain or other clinical indications and suitable for accepting N-methyl-d-aspartate receptor antagonists, glycine receptor beta (GLRB) modulators or alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) Methods for patients of therapy include determining an appropriate drug, an optimal dose per patient, and determining which patients are not suitable for receiving the therapy. Pharmacogenomic clinical decisions support the determination of a combination of targeted single nucleotide polymorphisms and clinical values, or targeted single nucleotide polymorphisms, targeted ketamine-specific expansion and contraction of topologically associated domains, and clinical values. The methods described herein allow for more efficient determination of which patients will experience drug efficacy and which patients will experience adverse drug events. The method provides personalized patient dose suggestions, drug administration frequency, and drug selection suggestions.

The present invention provides a pharmaceutical composition for use in treating cognitive decline. The pharmaceutical composition of the present invention comprises an antagonist of an AMPA receptor. The present invention also provides pharmaceutical compositions for use in treating a disease or condition associated with NMDA insensitivity in an NMDA-insensitive subject. The present invention can be useful, for example, in a subject in which intracellular calcium influx by stimulation with NMDA and glycine is inhibited in an NMDA receptor from which inhibition of activation by Mg ions has been released. The present invention further provides a pharmaceutical composition for use in treating overweight and obesity.

The pharmaceutical composition comprises the following components: (i) an AMPA receptor positive allosteric modulator (PAM) (e.g., an ampakine or a biarylpropylsulfonamide); and (ii) an NMDA receptor antagonist, e.g., ketamine or an analog thereof. Also described herein is a method for treating a psychiatric disorder or condition (e.g., depression, anxiety, substance use disorder, obsessive-compulsive disorder and related disorders, or a neurocognitive disorder), comprising administering a pharmacologic effective amount of components (i) and (ii) to a subject having a psychiatric disorder, wherein components (i) and (ii) may be administered to the subject as a single pharmaceutical composition in which the therapeutic compounds (i) and (ii) are present in a pharmacologic effective amount, or components (i) and (ii) are administered to the subject in separate doses within 48 hours or 24 hours of each other.

The present invention provides a pharmaceutical composition for use in treating cognitive decline. The pharmaceutical composition of the present invention comprises an antagonist of an AMPA receptor. The present invention also provides pharmaceutical compositions for use in treating a disease or condition associated with NMDA insensitivity in an NMDA-insensitive subject. The present invention can be useful, for example, in a subject in which intracellular calcium influx by stimulation with NMDA and glycine is inhibited in an NMDA receptor from which inhibition of activation by Mg ions has been released. The present invention further provides a pharmaceutical composition for use in treating overweight and obesity.

Methods for identifying patients diagnosed with treatment resistant or refractory depression, pain or other clinical indications who are eligible to receive N-methyl-D-aspartate receptor antagonist, glycine receptor beta (GLRB) modulator, or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-based therapies to include determining the appropriate medication, an optimal dose for each patient, and determining which patients are not eligible to receive the therapy. The pharmacogenomic clinical decision support assays include targeted single nucleotide polymorphisms and clinical values or a combination of targeted single nucleotide polymorphisms, targeted ketamine-specific expansion and contraction of topologically associated domains, and clinical values. The methods described herein allow for a more effective determination of which patients will experience drug efficacy and which patients will experience adverse drug events. The methods provide personalized patient recommendations for dose, the frequency of medication administration, and recommendations on drug choice.

Provided are compounds of Formula (I) which have shown utility in modulating AMPA receptor signaling and thus preventing AMPA receptor-mediated toxicity, which may find use in the treatment of diseases in which AMPA receptor activation plays a role in neurodegeneration, including the treatment of multiple sclerosis and other diseases.

The present disclosure relates to an application of a peptide in preparing drugs for treating and / or preventing cognitive impairment, belonging to the technical field of drugs for cognitive impairment. The present disclosure discloses an application of an artificially synthesized small molecule peptide in preparing drugs for treating and / or preventing cognitive impairment. When the peptide in the present disclosure is applied to cognitive impairment models, it may effectively play its biological role in blocking the binding between Synapsin IIb (Syn2b) and AMPA receptor subunit (GluA2), enabling the increase of GluA2 membrane expression, increase of AMPA current, enhancement of neuronal excitability and synaptic transmission, thereby alleviating learning and memory impairment in cognitive impairment model mice to some extent.

The invention relates to polypeptides derived from SCO-spondin for increasing or enhancing the basal excitatory synaptic transmission, notably glutamatergic neurotransmission. More particularly the invention relates to said polypeptides for increasing or enhancing glutamatergic neurotransmission in diseases or conditions comprising psychiatric disorders; drug addiction; viral infection (such as coronaviruses, e.g. SARS CoV2) related neurological symptoms; NMDA receptor (NMDAr) and / or AMPA receptor (AMPAr) deficiency related disease, notably anti-NMDAr encephalitis; vegetative state, and hypoxic brain injury. The present invention also relates to methods of treatment.

The present invention relates to use of a polypeptide in preparing a drug for treating and / or preventing cognitive disorder and belongs to the technical field of cognitive disorder drugs. Specifically disclosed is use of an artificially synthesized small-molecule polypeptide in preparing a drug for treating and / or preventing cognitive disorder. When applied to a cognitive disorder model, the small-molecule polypeptide can effectively exert the biological effect of blocking the binding of Synapsin IIb (Syn2b) to an AMPA receptor subunit (GluA2). This increases membrane insertion of GluA2, resulting in increased AMPA current, elevated neuronal excitability, and enhanced synaptic transmission, thereby relieving the learning memory damage of a cognitive disorder model mouse to a certain extent.

To provide a method and a computing device that allow for more effective determination regarding which patients will experience drug efficacy, and which patients will experience adverse drug events, and that provide personalized recommendations for patients regarding dose, the frequency of drug administration, and drug choice.SOLUTION: A method for identifying patients diagnosed with treatment resistant or refractory depression, pain or other clinical indications, who are eligible to receive N-methyl-D-aspartate receptor antagonist, glycine receptor beta modulator, or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-based therapies.SELECTED DRAWING: None

A pharmaceutical composition comprising the following components: (i) a positive allosteric modulator (PAM) of the AMPA receptor (e.g., an ampakine or biarylpropylsulfonamide); and (ii) an NMDA receptor antagonist, such as ketamine or an analogue thereof. Also described herein is a method for treating a mental disorder or condition (e.g., depression, anxiety, a substance use disorder, obsessive-compulsive and related disorders, or neurocognitive disorder), the method comprising administering to a subject having the mental disorder pharmaceutically effective amounts of components (i) and (ii), wherein components (i) and (ii) may be administered to the subject as a single pharmaceutical composition in which therapeutic compounds (i) and (ii) are present in pharmaceutically effective amounts, or components (i) and (ii) are administered to the subject in separate administrations within 48 or 24 hours of each other.

The invention belongs to the technical field of biological medicine, and discloses a synthesis method of aryl F-18 labeled sulfonyl chloride and application of the aryl F-18 labeled sulfonyl chloride in amine compound labeling, the method comprises the following steps: by taking a thiophenol derivative as a labeling precursor, obtaining an F-18 labeled thiophenol intermediate through photocatalytic aryl F-18 fluorination reaction; and then carrying out oxidative chlorination by using N-chlorosuccinimide to obtain aryl F-18 labeled sulfonyl chloride. The obtained aryl F-18 labeled sulfonyl chloride (4-[18F] fluorobenzene sulfonyl chloride) can be subjected to sulfonylation reaction with various amine compounds at room temperature, and the radiochemical conversion rate is as high as 98%; the method is successfully applied to novel synthesis of the AMPA receptor PET developer [18F] 2 (the conversion rate is 96% and is far higher than 13% reported in literature). The method is mild in reaction condition, high in conversion rate and wide in substrate application range, and an efficient method is provided for innovative preparation of the F-18 labeled PET probe.