87 results about "N-Methyl-D-aspartic acid" patented technology

A pain relief lollipop comprises a candy matrix comprising (a) an opioid agonist, (b) an N-methyl-D-aspartate receptor antagonist different from the opioid agonist, (c) gabapentin, or a pharmaceutically acceptable salt thereof, and, optionally, a muscle relaxant, sedative, anxiolytic, and/or antidepressant. A patient can self-administer small amounts of the pain relief drug as needed by simply licking or sucking on the lollipop in response to his subjective experience of pain.

Disclosed are novel compounds of the formula

or a pharmaceutically acceptable salt or solvate thereof, wherein

• • R¹, R², R³, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

An object of the present invention is to provide, for the case of implementing a therapeutic method in which at least two kinds of anti-dementia drugs are used together, a composition that has a good therapeutic effect on dementia, and also gives excellent compliance. Another object of the present invention is to provide a composition containing at least two kinds of anti-dementia drugs, in which release of the anti-dementia drugs from the composition is controlled, whereby a combined effect of the anti-dementia drugs can be achieved well. Still another object of the present invention is to provide a composition for which the frequency of administration and the amount taken are reduced and hence compliance can be improved, and a method of manufacturing such a composition. According to the present invention, there is provided a composition containing at least two kinds of anti-dementia drugs; such a composition containing at least one sustained-release portion containing an anti-dementia drug; and such a composition containing at least one cholinesterase inhibitor, and at least one N-methyl-D-aspartate receptor antagonist.

Compounds, composition and method for ameliorating alcohol or drug dependency withdrawal syndromes and withdrawal-induced brain damage are disclosed. In particular, a series of N-substituted-4-uredo-5,7-dihalo-2-carboxy quinoline compounds are disclosed having combined properties as antagonists of voltage-sensitive sodium channels (VSNaC) and as selective competitive antagonists at the strychnine-intensive glycine site of N-methyl-D-aspartate (NMDA) receptors. The disclosed compounds prevent or reduce the signs and symptoms of neurohyperexcitability and particularly the neurohyperexcitability associated with withdrawal syndrome manifested by patients upon withdrawal from chronic use of dependence inducing agents (e.g. ethanol, barbiturates, opiates etc.). The combined actions of the disclosed compound on VSNaC and NMDA receptors also impart properties to these compounds that are important in preventing and reducing excitotoxic neurodegeneration and reducing anxiety without the undesirable CNS depressant side-effects of agents hitherto employed for these purposes.

Methods of treating, mitigating, slowing the progression of, or preventing Alzheimer's Disease and Mild Cognitive Impairment (MCI) include administration of gonadotropin-releasing hormone analogs in combination with acetylcholinesterase inhibitors and/or N-methyl-D-aspartate receptor antagonists.

The invention relates to an N-methyl-D-aspartic acid preparation method. The N-methyl-D-aspartic acid preparation method comprises the following steps of: carrying out amino protection reaction by taking D-aspartic acid as a starting raw material to obtain amino protected D-aspartic acid, then carrying out Leuchart Wallanch reaction to obtain an N-methyl product, and then removing protecting groups with strong acid to obtain the N-methyl-D-aspartic acid in the end. The N-methyl-D-aspartic acid preparation method is mainly characterized in that the amino protection is carried out before amino methylation to solve the dimethylation problem, oxalaldehydic acid is used as a methylation reagent, the use of toxic and expensive reagents such as methyl iodide and dimethyl sulfate is avoided, and the high-purity product can be obtained without needing the complex purification process under the condition that the technology is safe, environment-friendly and inexpensive and has good yield.

Nontoxic substances that block the N-methyl-D-aspartate (NMDA) receptor, e.g., a morphinan such as dextromethorphan or dextrorphan, or that block a major intracellular consequence of NMDA-receptor activation, e.g., a ganglioside such as GM₁ or GT_1b, a phenothiazine such as trifluoperazine or a naphthalenesulfonamide such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, inhibit the development of tolerance to and/or dependence on addictive drugs, e.g., narcotic analgesics such as morphine, codeine, etc.

The present invention provides a method for modulating nicotinic/NMDA receptor function in a mammal in need of such treatment comprising administering a therapeutically effective amount of an agent that disrupts heterodimerization of α7 neuronal nicotinic acetylcholine receptors and N-methyl-D-asparate glutamate receptor. A polypeptide and fragments thereof comprising an amino acid sequence selected from the second intracellular loop of the α7 nAchR and carboxyl tail of the N-methyl-D-aspartate receptor are also provided, which are able to inhibit the heterodimerization. Also disclosed are nucleotide sequences encoding the polypeptides, and methods of inhibiting the heterodimerization of α7 nAchR and NMDAR using the polypeptides and nucleic acids.

Novel heterodimers of tetrahydroacridines and tetrahydroquinolinones are disclosed. The heterodimers are capable of acting as both acetylcholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. The heterodimers may be used to improve cognitive defects via treatment or prevention in both humans and non-humans.

Chronic pain is alleviated in a mammal suffering there from by administering to the mammal a chronic pain alleviating amount of a nontoxic N-methyl-D-aspartate receptor antagonist such as dextromethorphan, dextrorphan, ketamine or pharmaceutically acceptable salt thereof, in combination with a μ-opiate analgesic such as tramadol or an analogously acting molecular entity, and a methylxanthine such as caffeine, and optionally in sustained release dosage form.

Methods for prophylactically treating a stress-induced affective disorder or stress-induced psychopathology in a subject are provided. Also provided are methods for inducing and/or enhancing stress resilience in a subject. In certain embodiments, an effective amount, of an antagonist of the glutamate N-methyl-D-aspartate (NMDA) receptor, such as ketamine, or a pharmaceutically acceptable salt or derivative thereof, is administered to a subject prior to a stressor.

This invention relates to therapeutic compounds and compositions, and methods for their use in the prevention or treatment of neurological disorders. In particular, the invention relates to N-methyl-D-aspartate receptor (NMDAR) allosteric modulators and methods for their use in the prevention or treatment of disorders or conditions caused by or related to NMDAR dysfunctions. The invention also relates to a method for identifying NMDAR allosteric modulators.

For example, a piperidine derivative represented by following formula (I) (wherein, —C(═O)-Z- represents —C(═O)—CH₂—, —C(═O)—C(CH₃)₂—, —C(═O)—NH—, —C(═O)—O—, —C(═O)—S—, —C(═O)—CH₂CH₂—, —C(═O)—CH═CH—, —C(═O)—CH₂O—, —C(═O)—CH₂S—, —C(═O)—CH₂CH₂CH₂— or —C(═O)—NR⁸CH₂—; R¹ represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like; R² represents a hydrogen atom or hydroxy; R³ represents a hydrogen atom, substituted or unsubstituted lower alkyl, or the like; R⁵ represents a hydrogen atom, hydroxy, or the like; R⁶ represents a hydrogen atom, hydroxy, substituted or unsubstituted lower alkyl, or the like, etc.; R⁷ represents a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, or the like; n and k each independently represents an integer of 0 to 2; and ---- represents a single bond, or a double bond together with R⁴, where in case ---- is a single bond, R⁴ represents a hydrogen atom, hydroxy, or the like) or a pharmaceutically acceptable salt thereof and the like having an antagonistic activity for a glutamic acid receptor (NR2B/NMDA receptor) of an N-methyl-D-aspartic acid (NMDA) type containing an NR2B subunit are provided.

This invention is directed to substituted aryl compounds, which are linked to a substituted indole moiety by various linkers, and the kynurenine/kynuramine-like metabolites of these agents, their preparation and pharmaceutical compositions containing these compounds. This invention further is directed to the pharmaceutical use of the compounds for inhibiting GSK3β kinase and/or modulating N-methyl-D-aspartate (NMDA) channel activities for the treatment of neurodegenerative and other disorders.