289 results about "NR1 NMDA receptor" patented technology

Certain 1-aminoalkylcyclohexanes are systemically-active uncompetitive NMDA receptor antagonists having rapid blocking / unblocking kinetics and strong voltage-dependency and are therefore useful in the alleviation of conditions resulting from disturbances of glutamatergic transmission giving them a wide range of utility in the treatment of CNS disorders involving the same, as well as in non-NMDA indications, due to their immunomodulatory, antimalarial, anti-Borna virus, and anti-Hepatitis C activities and utilities. Pharmaceutical compositions thereof and a method-of-treating conditions which are alleviated by the employment of an NMDA receptor antagonist, as well as the aforementioned non-NMDA indications, and a method for the preparation of the active 1-aminoalkylcyclohexane compounds involved.

Topical compositions and methods for treating pain. The invention provides oil-in-water emulsions comprising an antidepressant; an NMDA-receptor antagonists; a lipophilic component; water; and a surfactant. The compositions induce a local-anesthetic effect when topically administered to intact skin thereby treating or preventing pain, for example, neuropathic pain.

A method of inhibiting the binding between N-methyl-D-aspartate receptors and neuronal proteins in a neuron is disclosed. The method comprises administering to the neuron an effective inhibiting amount of a peptide replacement agent for the NMDA receptor or neuronal protein interaction domain that effect said inhibition of the NMDA receptor—neuronal protein interaction. The method is of value in reducing the damaging effect of injury to mammalian cells. Postsynaptic density-95 protein (PSD-95) couples neuronal N-methyl-D-aspartate receptors (NMDARs) to pathways mediating excitotoxicity, ischemic and traumatic brain damage. This coupling was disrupted by transducing neurons with peptides that bind to modular domains on either side of the PSD-95 / NMDAR interaction complex. This treatment attenuated downstream NMDAR signaling without blocking NMDAR activity, protected cultured cortical neurons from excitotoxic insults, dramatically reduced cerebral infarction volume in rats subjected to transient focal cerebral ischemia, and traumatic brain injury (TBI) in rats.

The invention relates to a morphinan-derivative that targets NMDA receptors on pancreatic islets and has the general formula (I)whereinR1 is selected from —OH, —CO2H, —R0, —OR0, —OC(═O)R0, —OC(═O)OR0 or —OC(═O)NHR0; and R2 is selected from —H, —R0, —C(═O)R0, —C(═O)OR0, —C(═O)NHR0 or —C(═NH)—NH—C(═NH)—NH2; wherein R0 is in each case independently selected from —C1-C6-alkyl, -aryl, -heteroaryl, —C1-C6-alkyl-aryl or —C1-C6-alkyl-heteroaryl, in each case independently unsubstituted or substituted;or its physiologically acceptable salt and / or stereoisomer, including mixtures thereof in all ratios, for use in the treatment of a disease or condition, where the disease or condition is insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, obesity, and / or diabetic nephropathy.

The invention provides methods and compositions for administering an NMDA receptor antagonist (e.g., memantine) to a subject.

Coupling of excitation to neurogenesis in proliferating post-natal NPCs is demonstrated in vitro and in vivo. Neurogenesis is potently enhanced by excitatory stimuli, and involves Cav1.2 / 1.3 channels and NMDA receptors. These Ca2+ influx pathways are located on the proliferating NPCs, allowing them to directly sense and process excitatory stimuli. Excitation increases the fraction of NPC progeny that are neurons, and increases total neuron number. Signaling in this pathway leads to rapid induction of a proneural gene expression pattern involving the bHLH genes HES1, Id2, and NeuroD, and the resulting cells become fully functional neurons defined by neuronal morphology, expression of neuronal structural proteins, expression of neuronal TTX-sensitive voltage gated Na+ channels, and synaptic incorporation into active neural circuits.

The invention relates to methods for the prevention and / or treatment of tinnitus induced by cochlear excitotoxicity. In these methods, a pharmaceutical composition comprising an NMDA receptor antagonist is administered to an individual in need of such treatment by appropriate devices and / or formulations for local administration to the inner ear. The tinnitus to be prevented and / or treated may be provoked by acoustic trauma, presbycusis, ischemia, anoxia, treatment with one or more ototoxic medications, sudden deafness, or other cochlear excitotoxic-inducing occurrence. The invention also relates to method for the identification of compounds effective in the treatment and prevention of tinnitus by a novel screening method incorporating an electrophysiological test method.

Topical compositions and methods for treating pain. The invention provides oil-in-water emulsions comprising an antidepressant; an NMDA-receptor antagonists; a lipophilic component; water; and a surfactant. The compositions induce a local-anesthetic effect when topically administered to intact skin thereby treating or preventing pain, for example, neuropathic pain.

The present invention is directed to pharmaceutical compositions of effective amounts of NMDA receptor antagonists and preservative for the administration to a patient in need of effective analgesia and anesthesia. The compositions of the invention advantageously do not cause any significant neurotoxicity. The preferred NMDA receptor antagonist is ketamine. The preferred preservative is benzalkonium chloride.

The invention provides a method, and dosage form therefor, of treating impaired motor function associated with Parkinson's disease, anti-Parkinson's drug treatment, e.g. L-Dopa therapy, and / or dementia associated with Parkinson's disease. The invention includes the combined administration of an NMDA receptor antagonist and an antidepressant, e.g., the combination of amantadine and citalopram or venlafaxine, or an NMDA receptor antagonist and an anxiolytic agent, e.g., amantadine and buspirone or trazodone, for the amelioration of undesired tremors, akinesia, dyskinesia, or bradykinesia associated with one or more different disorders or diseases. The drugs can be included in a single dosage form. One embodiment includes a combination dosage form containing each drug in controlled release forms. Another embodiment includes a combination dosage form providing a controlled release of an NMDA receptor antagonist and a rapid release of a neuroactive agent after administration to a subject.

The invention relates to methods for the prevention and / or treatment of tinnitus induced by cochlear excitotoxicity. In these methods, a pharmaceutical composition comprising an NMDA receptor antagonist is administered to an individual in need of such treatment by appropriate devices and / or formulations for local administration to the inner ear. The tinnitus to be prevented and / or treated may be provoked by acoustic trauma, presbycusis, ischemia, anoxia, sudden deafness, or other cochlear excitotoxic-inducing occurrence.

The invention provides compositions and methods for treating autoimmune diseases such as multiple sclerosis. The compositions include a combination of an NMDA Receptor antagonist, such as memantine or rimantadine, and a fumarate agent, such as dimethyl fumarate.

The present invention provides compositions and methods for enhancing cognitive function and synaptic plasticity. According to the method, Ca++ influx into excitatory neurons (nerve cells) is decreased by treatment with a number of different agents including divalent cations (e.g., Mg++), GABAB agonists, GABAA agonists, calcium channel blockers, and / or compounds that decrease action potential firing such as sodium channel blockers. Decreasing Ca++ influx results in increased synaptic plasticity and enhanced cognitive function. In particular, decreasing Ca++ influx associated with uncorrelated neural activity results in long-lasting increases in synaptic plasticity and cognitive function. This is achieved by administration of agents that cause a voltage-dependent block of NMDA receptors (e.g., divalent cations such as Mg++) or by administration of GABAB agonists such as baclofen. The invention further provides screening methods useful in identifying compounds that enhance synaptic plasticity and cognitive function.

The invention provides methods and compositions for administering an NMDA receptor antagonist (e.g., memantine) to a subject.

The invention relates to the use of NMDA receptor antagonists such as 1-aminocyclohexane derivatives to modify deposition of potentially toxic and fibrillogenic Aβ peptides in amyloidopathies. Specifically, the invention relates to the ability of memantine to intervene in the processing of APP and decrease the levels of fibrillogenic Aβ peptides.

A drug that inhibits NMDA receptors (such as ketamine, a surgical anesthetic) is continuously administered to patients suffering from neuropathic pain. Unless the NMDA antagonist drug has inherent safening activity, this treatment requires a “safener” drug to prevent the neurotoxic side effects of NMDA antagonists. One class of safener drugs that increase the efficacy of the treatment include alpha-2 adrenergic agonists, such as clonidine. The treatment lasts for several days and nights, continuously. A maximum tolerated dosage is titered for each patient, such as by observing slurring of speech, and the patient does not lose consciousness except during normal sleep. Magnesium and / or drugs that inhibit ketamine-degrading enzymes can also be used. Patients who suffered for years from chronic intractable pain emerged from this treatment with apparently permanent relief, or with lasting reductions in their levels of pain.

The present embodiments relate to topically delivered compounded medications. A transdermal cream may provide the effective topical administration of multiple medications simultaneously; may include low concentrations of local anesthetics, a NSAID, an anticonvulsant, and / or other active ingredients; and may include lidocaine, prilocaine, meloxicam, and lamotrigine and / or topiramate. Alternatively, the transdermal cream may include a lidocaine / prilocaine base cream to which is added a fine powder of one or more ground up medications to form a compounded medication. The compounded medication in powder form may be generated from grinding up tablets of NSAIDs, anticonvulsants, nerve depressants, antidepressants, muscle relaxants, NMDA receptor antagonists, opiate or opioid agonists, and / or other agents. The compounded medication in powder form may include meloxicam, lamotrigine, topiramate, other active ingredients, and DMSO or Sterile Water for Irrigation. In another aspect, the present embodiments relate to methods of compounding medications and transdermal creams or gels.

Improved treatments of joint diseases, such as, e.g. osteoarthritis and rheumatoid arthritis, and pain, wherein a strontium-containing compound is administered alone or in combination with one or more second therapeutically and / or prophylactically active substances, selected from the group consisting of bisphosphonates, glucosamine, pallitative agents, analgesic agents, disease modifying anti-rheumatic compounds (DMARDs), selective estrogen receptor modulators (SERMs), aromatase inhibitors, non-steroidal anti-inflammatory agents (NSAIDs), COX-2 inhibitors, COX-3 inhibitors, opioids, inhibitors / antagonists of IL-1, inhibitors / antagonists of TNF-alpha, inhibitors of matrix metallo-proteinases (MMPs), cathepsin K inhibitors, inhibitors / antagonists of RANK-ligand, statins, glucocorticoids, chondroitin sulphate, NMDA receptor antagonists, inhibitors of interleukin-I converting enzyme, Calcitonin gene related peptide antagonists, glycine antagonists, vanilloid receptor antagonists, inhibitors of inducible nitric oxide synthetase (iNOS), N-acetylcholine receptor agonists, neurokinin antagonists, neuroleptic agents, PAR2 receptor antagonists and anabolic growth factors acting on joint tissue components. Pharmaceutical compositions comprising a strontium-containing compound and a second therapeutically and / or prophylactically active substance as defined above.

A methods, kits and compositions for diagnosing a central nervous system disorder, particularly transient ischemic attack or stroke, comprising measuring the level of NR2A and / or NR2B NMDA receptor or fragment thereof, in a biological sample from a human subject, and optionally measuring other biomarkers such as homocysteine and glutamate. The method is particularly useful for identifying individuals that are at risk for stroke, and for diagnosing stroke in an emergency room setting.

The invention relates to transdermal therapeutic systems (TTS) which include, as active ingredient, the NMDA receptor antagonist memantine or one of its physiologically compatible salts. The TTSs can be produced and used for treating diseases of the central nervous system.

Tension-type headache is treated by interacting smith neuronal transmission in relation to pain in connection with headache in a way which prevents or decreases sensitization of second order nociceptive neurons. In particular, treatment is performed by administration of an effective amount of a substance which prevents or decreases central sensitization. Important examples of such substances are substances which interact with glutamate neurotransmission, such as glutamate receptor antagonists, such as NMDA receptor antagonists, such as MK-801 or Amitriptylline or Imipramine or Desipramine or Mirtazaprine or Venlafaxine. Other examples are substances which interact with nitric oxide, such as nitric oxide synthase (NOS) inhibitors, such as L-NMMA or L-NAME or L-NIO or L-NNA. According to a broader aspect of the invention tension-type headache is treated by administration of substances which are effective in preventing or decreasing pain in connection with tension-type headache, such as the substances mentioned above. An additional aspect of the invention relates to treatment of tension-type headache by administration of substances which substantially inhibit the activity of nitric oxide synthase (NOS), such as NOS inhibitors, such as L-NMMA or L-NAME or L-NIO or L-NNA.

The present invention describes a novel treatment for movement disorders, including tardive dyskinesia, tic disorders, Tourette's syndrome, and blepharospasm, and other focal dystonias. The treatment of the present invention utilizes agents that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate. Alternatively, separate agents having these activities can be combined and administered together. The invention also provides a third agent that acts as a non-competitive NMDA-receptor blocking agent or ion channel blocker that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium. Alternatively, magnesium can be administered alone for prevention and treatment of movement disorders.

The disclosure relates, at least in part, to methods of treating autism in a patient in need thereof by administering an effective amount of a disclosed compound, e.g., a NMDA receptor glycine site partial agonist.

The invention relates to formulations and methods for preventing and / or treating substance abuse, addiction, withdrawal symptoms, and anticipation associated with substance abuse. In particular the invention relates to formulations comprising at least one processed Morinda citrifolia L. product, and methods comprising the administration of at least one processed Morinda citrifolia L product to prevent and / or treat substance abuse, addiction, withdrawal symptoms, and anticipation associated with substance abuse in living organisms. Embodiments of the invention further comprise Morinda citrifolia based nutraceuticals and administration thereof to affect regulation of dopamine levels, inhibition of opioid receptors, inhibition of mu opioid receptors, inhibition of kappa opioid receptors, inhibition of delta opioid receptors, acting as NMDA antagonist, inhibition of sensitization of NMDA receptors, and / or acting as opiate antagonists.

Cannabinoids have been found to have antioxidant properties, unrelated to NMDA receptor antagonism. This new found property makes the cannabinoids useful in the treatment and prophylaxis of wide variety of oxidation associated diseases, such as ischemic, age-related, inflammatory and autoimmune diseases. The cannabinoids are found to have particular application as neuroprotuctants, for example in limiting neurological damage following ischemic insults, such as stroke and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and HIV dementia. Nonpsychoactive cannabinoids, such as cannabidoil, are particularly advantageous to use because they avoid toxicity that is encountered with psychoactive cannabinoids at high doses useful in the method of the present invention. A particular disclosed class of cannabinoids useful as neuroprotective antioxidants is formula (I) wherein the R group is independently selected from the group consisting of H, CH3, and COCH3

The present invention relates to compositions and methods for treating a human patient afflicted with a neuropsychiatric disorder. Specifically, the invention provides for compositions and methods of modulating or antagonizing the activity of neuronal NMDA receptors, wherein such antagonistic activity is capable of modulating the glutamate induced excitatory response of the neurons, thereby inhibiting an excitotoxic effect, promoting a neurotrophic effect, and thereby providing a therapeutic effect that treats the neuropsychiatric disorder.

Disclosed herein are substituted cyclohexanone-based NMDA receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

A method for treating pain in painful diabetic neuropathy comprises administering in combination a first agent that comprises a compound as defined herein, illustratively lacosamide, and a second agent effective to provide enhanced treatment of pain, by comparison with the first agent alone. The second agent illustratively comprises an analgesic, an anticonvulsant, an antidepressant or an NMDA receptor antagonist.