105 results about "GABAA receptor" patented technology

The invention is directed to novel 17β-heteroaryl substituted steroids of Formula I, pharmaceutical compositions thereof, and their use as modulators of GABA_A receptors.

Compounds of Formula (1) are provided, as are methods for their preparation. The variables Z₁, Z₂, Z₃, R₄, R₅, R₆, R₇, R₈, and Ar in the above Formula are defined herein. Such compounds may be used to modulate ligand binding to GABA_A receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals, and livestock animals. Compounds provided herein may be administered alone or in combination with one or more other CNS agents to potentiate the effects of the other CNS agent(s). Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting GABA_A receptors (e.g., receptor localization studies).

Disclosed are compounds of the formula: and the pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X, A, B, C, D and W are defined herein, which compounds bind with high selectivity and high affinity to the benzodiazepine site of the GABAA receptors and are therefore useful in the treatment of certain central nervous system (CNS) diseases and as probes for the localization of GABAA receptors in tissue samples.

Novel analogs and prodrugs of the loop diuretic bumetanide are described. Pharmaceutical compositions containing bumetanide analogs and prodrugs are also described. These analogs and prodrugs are particularly useful for the treatment and/or prophylaxis of conditions that involve the NKCC cotransporter family (NKCC1 and NKCC2), or the KCC cotransporter family (KCC1, KCC2, KCC3, KCC4), or GABAa receptors. Such conditions include, but are not limited to anxiety disorders, epilepsy, migraine, non-epileptic seizures, sleep disorders, obesity, eating disorders, autism, depression, edema, glaucoma, stroke, ischemia, neuropathic pain, addictive disorders, schizophrenia, psychosis, and tinnitus.

Provided herein are methods, drug formulations, and dosing regimens for improving cognitive function in a normal or cognitively impaired subject. For instance, methods provided herein comprise administering a GABA_A receptor antagonist so that peak concentration of the GABA_A receptor antagonist occurs when the subject is asleep.

The present invention relates to novel benzimidazole derivatives, pharmaceutical compositions containing these compounds, and methods of treatment therewith. The compounds of the invention are useful in the treatment of central nervous system diseases and disorders, which are responsive to modulation of the GABA^A receptor complex, and in particular for inducing and maintaining anesthesia, sedation and muscle relaxation, as well as for combating febrile convulsions in children. The compounds of the invention may also be used by veterinarians.

The present invention relates to novel imidazo[1,2-a]pyridine compounds of general formula (I):

as well as pharmaceutically acceptable salts thereof; wherein R₁, R₂, R₃ and R₄ are as defined in the claims. The compounds have specific affinity for GABA_A receptor and are therefore useful in the treatment and prevention of diseases modulated by α₁- and α₂-GABA_A receptors.

The invention provides compounds as shown in a general formula (I) which is described in the specification and cis-trans-isomers, enantiomers, diastereomers, racemes, solvates, hydrates, pharmaceutically acceptable salt and esters thereof. The invention further provides preparation method for the compounds, pharmaceutical compositions of the compounds and application of the compounds as modulators for an alpha5-GABAA receptor. T, Z, A and Y in the formula (I) are as defined in the specification.

The invention relates to a novel multi step process of making compounds of Formula I:

wherein R¹ is an alkoxy group and R² is an optionally substituted, N-attached heteroaryl. The hydrogen at the 5-position can be α or β isomer, preferably α. Preferably the compound of Formula I is 17β isomer. The invention also relates to novel 3α-hydroxy-3β-substituted-17-substituted steroid compounds having GABA_A receptor modulating activity, pharmaceutical compositions comprising these compounds, and the use of these compounds in a method of modulating brain excitability.

Substituted imidazolylmethyl pyridine and pyrazine derivatives that bind to GABA_A receptors are provided. Such compounds may be used to modulate ligand binding to GABA_A receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals and livestock animals. Compounds provided herein may be administered alone or in combination with one or more other CNS agents to potentiate the effects of the other CNS agent(s). Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting GABA_A receptors (e.g., receptor localization studies).

This invention relates to heteroaryl substituted fused bicyclic heteroaryl compounds, such as heteroaryl substituted imidazopyridines, imidazopyrazines, imidazopyridizines, imidazopyrimidines, and imidazothiazoles, which may be described by Formula I or Formula II:

The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABA_A receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Processes for preparing compounds of Formula I and Formula II are disclosed.

This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I or Formula II in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABA_A receptors in tissue sections.

The present invention provides methods for treating anxiety or irritability in a subject. The methods comprise administering to the subject an effective amount of an antagonist of allopregnanolone (THP), or a regulator which decreases expression of the alpha 4 subunit of GABA such as gabadoxbol (THIP), or a vector comprising an isolated nucleic acid molecule encoding a mutant alpha 4 subunit GABA_A receptor protein having a neutral or non-basic amino acid residue substituted for the arginine residue at position 353 of the wild type mature protein, wherein this nucleic acid molecule is operably linked to a promoter which functions in the human brain. Such methods are useful in treating a subject undergoing a stage such as entering or having reached puberty, suffering from pre-menstrual syndrome (PMS), entering or having reached post-partem stage, entering or having reached menopause, and/or suffering from chronic stress. Also provided by the present isolated is a mutant alpha 4 subunit of GABA_A receptor protein which has a neutral or non-basic amino acid residue substituted for the arginine residue at position 353 of the wild type mature protein and an isolated nucleic acid molecule encoding this mutated protein. The present invention also provides vectors comprising a subject isolated nucleic acid molecule operably liked to a promoter which functions in prokaryotic or eukaryotic cells, as well as host cells comprising such vectors. In addition, the present invention provides methods for identifying an antagonist of THP.

The present invention relates to methods of and compositions for treating and relieving symptoms and disease associated with indications caused by a physiological drive to alleviate a sensation of anxiety. In one treatment method, methods of, and compositions for, modulating the expression of certain GABAA receptor subunits are used to treat anxiety-related disorders and depressive disorders associated with physiological tolerance to endogenous neurosteroids.

Compounds of Formula I and Formula II are provided, as are methods for their preparation. The variables Y, Z₁, Z₂, Z₃, R₄, R₅, R₆, R₇, R₈ and Ar in the above formula are defined herein. Such compounds may be used to modulate ligand binding to GABA_A receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals and livestock animals. Compounds provided herein may be administered alone or in combination with one or more other CNS agents to potentiate the effects of the other CNS agent(s). Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting GABA_A receptors (e.g., receptor localization studies).

This invention relates to novel imidazole derivatives of the general formula (I): pharmaceutical compositions containing these compounds, and methods of treatment therewith. The compounds of the invention are useful in the treatment of central nervous system diseases and disorders, which are responsive to modulation of the GABA_A receptor complex, and in particular for combating anxiety and related diseases.

The present disclosure provides a pharmaceutical preparation of a compound of formula (I) or a stereoisomer, pharmaceutically acceptable salt, or prodrug thereof. The present disclosure further provides a method for general anesthesia or sedation for mammals. Also provided are kits and manufactured products of the medicament and the pharmaceutical composition and a method for using the medicament and the pharmaceutical composition.

Disclosed are 1H-Pyrrolo[3,2-b]pyridine-3-carboxylic acid amides that bind to the benzodiazepine site of GABAA receptors. Such compounds can be used to modulate ligand binding to GABAA receptors in vivo and in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals, and livestock animals.