86 results about "AMPA receptor activity" patented technology

Methods for increasing the level of neurotrophic factors and neurotrophic factor receptors in the brain of a mammal afflicted with a pathology which produces neurodegeneration without significant loss of memory or learning comprising administering to a mammal an effective amount of an allosteric upmodulator of alpha -amino-3-hydroxy-5-methyl-isoxazole-4-proprionic acid (AMPA) receptors.

The present invention provides 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid compounds and their addition salts, and processes for preparing them, which have antagonism against excitatory amino acid receptors, in particular, an AMPA receptor. The 6,7-asymmetrically disubstituted quinoxalinecarboxylic acid compounds and their addition salts of the present invention are represented by formula (1)wherein Q, R, R1 and R2 are as described in the specification.

The present invention relates to a therapeutic agent for dyskinesia excluding tremor, comprising 1,2-dihydropyridine compound, a salt thereof, or a solvate thereof, which shows AMPA receptor antagonism and is highly useful as a pharmaceutical drug.

The invention relates to novel quinazolines and heterocycles which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating, preventing or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, myoclonus. Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition and learning enhancers.

The invention is directed to a method for alleviating respiratory depression in a subject as a result of disease of pharmacological agents such as opiates, opioids or barbiturates. The invention also discloses pharmaceutical compositions for use with the method, the composition containing in combination, an analgesic, anaesthetic, or a sedative and a positive allosteric AMPA receptor modulator in an amount sufficient to reduce or inhibit respiratory depression caused by the analgesic, anaesthetic, or sedative.

Provided is a compound having an AMPA receptor function enhancing action, and useful as a prophylactic or therapeutic drug for depression, Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder (ADHD) and the like. A compound represented by the formula (I):

Methods for modulating the endocrine system of a mammal are provided. In the subject methods, a positive allosteric modulator of AMPA receptors of the hypothalamus are administered to the host. The subject methods find use in applications where it is desired to increase the baseline circulatory level of a growth hormone in a mammalian host. The subject methods also find use in applications where it is desired to increase the circulatory level of DHEA in a mammalian host. Finally, another subject method also finds use in applications where it is desired to decrease the circulatory level of cortisol in a mammalian host.

The invention belongs to the technical field of medicines and particularly relates to a perampanel sesquihydrate and a preparation method thereof. The perampanel sesquihydrate contains one and a half crystal water. The perampanel sesquihydrate has the advantages that the purity is high; the stability is good, and the moisture absorption and the weight increment are not obvious even at a high humidity condition; by virtue of the perampanel sesquihydrate, the inhibiting effect to the activity of AMPA receptor glutamic acid is increased by about 20%. The invention further relates to application of a composition of the perampanel sesquihydrate in the treatment of neuropsychiatric diseases.

It is an object of the present invention to provide a novel therapeutic agent for glioblastoma. In accordance with the present invention, it was found that compounds having an antagonistic action against AMPA receptor are useful as therapeutic agents for glioblastoma, particularly primary glioblastoma de novo with a high malignancy level, and the object has been attained.

This invention relates to methods of use for AMPA receptor potentiator compounds and pharmaceutical compositions in the prevention and treatment of cognitive impairment as a result of acute or chronic sleep deprivation, including enhancement of receptor functioning at synapses in brain networks responsible for higher order behaviors. A still further aspect of the present invention is the use of an active agent as described above for the preparation of a medicament for the treatment of a disorder as described above.

Antagonists of group 1 metabotropic glutamate receptors (mGluR) potentiate the effect of positive AMPA receptor modulators on neurotrophin expression, such as brain-derived neurotrophic factor (BDNF). The findings described herein suggest a combinatorial approach for drug therapies, using both positive AMPA receptor modulators and mGluR antagonists. to enhance brain neurotrophism.

The present invention is based on the discovery that neuronal pentraxins play a role in the clustering and internalization of AMPA receptors, synaptogenesis, and metabotropic glutamate receptor-mediated long term depression (LTD) of a synapse. Accordingly, there are provided methods of identifying compounds that that modulate mGluR-mediated AMPA receptor internalization and LTD. Further provided are cleavage products of a member of the neuronal pentraxin family, neuronal pentraxin receptor (NPR). Also provided are isolated peptides comprising the Narp association regions 1 and 2 (NAR1 and NAR2, respectively) and the Narp binding motif (NBM) of AMPA receptors. Finally, there are provided antibodies that block binding of neuronal pentraxins to AMPA receptors, in particular, antibodies that bind NAR1, or NAR2, or NBM.

The invention belongs to the field of organic synthetic medicines, and concretely relates to a small molecular oxothiazine derivative. The general formula is shown in the specification. The small molecular oxothiazine derivative can be used as a forward allosteric regulator of an AMPA receptor, and the compound is proved to be capable of positively regulating the AMPA receptor, so that the conformation after an agonist (such as endogenous neurotransmitter glutamic acid) is combined with the receptor is more stable, the inactivation rate of the receptor is reduced, the desensitization of the receptor is inhibited, and the function of the AMPA receptor is enhanced.

The invention discloses a short peptide blocking long-term synaptic potentiation (LTP) and application thereof and belongs to the field of biological chemistry. A bioinformatics method is adopted to analyze human homologous sequences of different species of AMPA receptor subunits GluR2, it is found that a high conserved domain exists at the terminal C of GluR2, and the short peptide is designed on the basis and further comprises a short peptide modification peptide having cytomembrane penetrating capacity and a short peptide modification peptide marked with a fluorescent group. Amino acid sequences of the short peptide are shown as SEQ ID NO.1 and SEQ ID NO.2. The short peptide or the short peptide modification peptide can block LTP expression and has no influence on functions of LTD and NMDA receptors having synaptic plasticity. Therefore, the short peptide or the short peptide modification peptide is applied to preparation of drugs for treating or preventing diseases related to glutamic acid overexcitation diseases and pathological synaptic plasticity LTP, or establishment of experimental animal models of the diseases related to glutamic acid overexcitation diseases and the pathological synaptic plasticity LTP.

The present invention provides methods of treating and pharmaceutical compositions useful for treating a mood disorder or depressive symptoms associated with pain, inducing analgesia and treating pain in a subject by administering a pharmaceutically effective amount of an agent capable of one or more of increasing GluA1 level, expression, concentration, or biological activity, increasing calcium permeable AMPA (α amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor (CPAR) level, expression, concentration, or biological activity or potentiating a CPAR current. The agent may be an AMPA potentiator or ampakine. The agent may increase AMPA receptor currents by slowing the deactivation of open channels and may be, for instance, 2-pyrrolidinone, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide (PEPA) or LY451646. The agent may also be a protein, RNA or DNA product.

The invention provides compounds of the formula (I): wherein R¹ and R² 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.

Method for identifying a compound useful for the therapeutic treatment of a neurological disease or disorder such as stroke, head trauma, spinal cord injury, epilepsy, anxiety, or neurodegenerative diseases such as Alzheimer's Disease, Huntington's Disease or Parkinson's Disease, or useful as a muscle relaxant, analgesic, or adjuvant to general anesthetics. The compounds is active on a receptor-operated calcium channel, including, but not limited to, that present as part of an NMDA receptor-ionophore complex, a calcium-permeable AMPA receptor, or a nicotinic cholinergic receptor, as a noncompetitive antagonist. The method includes identifying a compound which bonds to the receptor-operated calcium channel at the site bound by the arylalkylamines Compound 1, Compound 2 or Compound 3.

The present invention provides AMPAR excitotoxicity mediating polypeptides comprising the GluR2 NT1-3-2 (Y142-K172) amino acid sequence (SEQ ID NO:1) or the GAPDH(2-2-1-1) (I221-E250) amino acid sequence (SEQ ID NO:2). Also disclosed are nucleotide sequences encoding the polypeptides, methods of inhibiting GAPDH association with the GluR2 subunit or p53. Methods of inhibiting AMPA receptor mediated excitotoxicity using the polypeptides and nucleic acids are also disclosed.