41 results about "Dopamine receptor D1" patented technology

The invention provides a new method of treating diseases or conditions characterized by reduced dopamine D1 receptor signaling activity, such as Parkinson's disease, depression, and cognitive impairment of schizophrenia, comprising administering an effective amount of a 1,3,5,-substituted, 6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-one to a patient in need thereof.

The present invention relates to novel functionally selective ligands of dopamine D2 receptors, FIG. 1 including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.

The invention features combinations of dopaminergic agents and analgesic agents useful for treating pain. In particular, the combinations feature a low ratio of dopaminergic agent to analgesic agent. The dopaminergic agent can be an agonist of the dopamine receptor D1-like family or the dopamine receptor D2-like family. Such combinations potentiate analgesia to 1) alleviate acute pain, 2) prevent the transition from acute pain to chronic pain, and 3) manage chronic pain.

The present invention provides a panel of at least five clinical analyses or tests (using serum samples) to determine the risk of pediatric acute-onset neuropsychiatric syndrome (PANS) and/or pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) in an individual. These include enzyme linked immunosorbent assays (ELISAs) to measure antibody titers against neuronal antigens present in the brain; the neuronal antigens include lysoganglioside, tubulin, dopamine receptor D1, dopamine receptor D2, serotonin receptor 5HT2A, and serotonin receptor 5HT2C. Antibody titers against at least four of these neuronal antigens are required in the present methods; preferably antibody tiers against all of these neuronal antigens are measured. A final assay is used to quantify calcium/calmodulin-dependent protein kinase activity using a neuronal cell line. The results of these analyses or tests are then combined using an algorithm to determine whether a PANS or PANDAS diagnosis is appropriate for the individual. Depending on the diagnosis, an appropriate treatment can be determined.

The present invention relates to a composition for modulating the activation of Nurr1, the composition comprising an agonist or an antagonist of a dopamine D2 receptor, methods for modulating the activation of Nurr1 by the dopamine D2 receptor, a method and composition for treating Nurr1-related diseases using the dopamine D2 receptor, and methods for screening a modulator of a dopamine D2 receptor of a test compound. Accordingly, the activation of Nurr1 can be modulated by treating the dopaminergic neurons with the agonist or the antagonist of the dopamine D2 receptor, thereby enhancing or inhibiting generation of the dopaminergic neurons.

The present invention relates to an aminomethyl substituted bicyclic aromatic compound of the formula I

wherein

• • Ar is a cyclic radical selected from the group consisting of phenyl, a 5- or 6-membered C-bound heteroaromatic radical comprising as ring member 1, 2 or 3 heteroatoms which are, independently of each other, selected from O, S and N, and a phenyl ring fused to a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, where the heterocyclic ring comprises as ring members 1, 2 or 3 heteroatoms selected from N, 0 and S and/or 1, 2 or 3 heteroatom-containing groups each independently selected from NR⁸, where R⁸ is H, C₁-C₄-alkyl, fluorinated C₁-C₄-alkyl, C₁-C₄-alkylcarbonyl or fluorinated C₁-C₄-alkylcarbonyl, and where the cyclic radical Ar may carry 1, 2 or 3 substituents R^a, wherein the variable R^a has the meanings given in the claims and in the description;
  • X is a covalent bond or N—R², CHR², CHR²CH₂, N or C—R²;
  • Y is N—R^2a, CHR^2a, CHR^2aCH₂ or CHR^2aCH₂CH₂;
  • is a single bond or a double bond;
  • E is CH₂ or NR³;
  • R¹ is H, C₃-C₄-cycloalkyl, C₃-C₄-cycloalkylmethyl, C₃-C₄-alkenyl, fluorinated C₁-C₄-alkyl, fluorinated C₃-C₄-cycloalkyl, fluorinated C₃-C₄-cycloalkylmethyl, fluorinated C₃-C₄-alkenyl, formyl or C₁-C₃-alkylcarbonyl;
  • R^1a is H, C₁C₄-alkyl, C₃-C₄-cycloalkyl, C₃-C₄-alkenyl, fluorinated C₁-C₄-alkyl, fluorinated C₃-C₄-cycloalkyl, fluorinated C₃-C₄-alkenyl,
  • R² and R^2a each independently are H, CH₃, CH₂F, CHF₂ or CF₃ or R^1a and R² or R^1a and R^2a together are (CH₂)_n with n being 1, 2 or 3;
  • R³ is H or C₁C₄-alkyl;
  • R⁴ and R⁵ independently of each other are H, C₁-C₄-alkyl, fluorinated C₁-C₄-alkyl or C₁-C₄-alkoxy or may form, together with N, a 4-, 5- or 6-membered saturated or unsaturated ring;
  • R⁶ and R⁷ independently of each other are H or halogen;

and the physiologically tolerated acid addition salts thereof.

The invention belongs to the field of pharmacy, relates to medicinal use of an indole piperazine derivative, and in particular relates to appetency of the indole piperazine derivative to dopamine D3 receptor and 5-HT1A and 5-HT2A receptors, function characteristics and use in preparation of medicines for nervous system disease; adrenergic beta-2 receptor crystal structure is used as a template for the construction of a dopamine 5-HT1A receptor model; by accuracy verification on the receptor model and molecular dynamics simulation, a flexible receptor conformation can be obtained; active sites of the flexible receptor conformation can be detected; detection results are superimposed and a dynamic receptor effective-mass model is constructed; an existing compound database is screened and the activity is tested; and results show that the screened compound FDFWHF003 and its derivatives have good activity to the dopamine receptor and 5-HT receptors, can be used for preparation of anti-schizophrenia medicines, and especially is suitable for the preparation of medicines for treating schizophrenia caused by dopamine system and 5-HT system functional disorders.

The invention discloses a fluoride-18 marked dopamine D4 receptor developing agent and a preparation method thereof. The fluoride-18 marked dopamine D4 receptor developing agent is 2-[4-(4-[<18>F] fluorobenzyl) piperazine-1-yl methyl] pyrazolo [1, 5-alpha] pyridine, and the structural formula of the developing agent is shown in a formula (I). The preparation method comprises three steps of: step one, reacting pyrazolo [1, 5-alpha] pyridine-2-formaldehyde with N-formoxyl piperazine to generate 2-[4-piperazine formaldehyde-1-yl methyl) pyrazolo [1, 5-alpha] pyridine; step two, hydrolyzing 2-[4-piperazine formaldehyde-1-base methyl) pyrazolo [1, 5-alpha] pyridine under a strong acidic condition to generate 2-[4-piperazine-1-yl methyl) pyrazolo [1, 5-alpha] pyridine; and step three, reacting 2-[4-piperazine-1-yl methyl) pyrazolo [1, 5-alpha] pyridine with 4-[<18>F] fluorobenzaldehyde to generate a target molecule. 2-[4-(4-[<18>F] fluorobenzyl) piperazine-1-yl methyl] pyrazolo [1, 5-alpha] pyridine prepared by the method can be used for dopamine D4 receptor development and is a specific dopamine D4 receptor developing agent.

The present invention provides compounds, compositions and methods for inhibiting D2R-DISC1 interaction. Specifically, the present invention provides a polypeptide comprising the amino acid sequence KIYIVLRRRRKRVNT (SEQ ID NO: 1) or SEQ ID NO:5, a fragment thereof, or a polypeptide comprising an amino acid sequence that is at least 80% identical to SEQ ID NO: 1 or 5, or a fragment thereof, wherein the polypeptide is not a naturally occurring dopamine receptor. Also provided is a method of identifying an agent that inhibits the interaction of D2R with DISC1, a method of identifying an agent that binds to the polypeptide sequence defined by SEQ ID NO: 1 or 5, and a method of inhibiting D2R interaction with DISC1 in a mammal comprising administering an agent that inhibits the interaction of D2R with DISC1 to the mammal.

The present invention relates to 6-amino(aza)indane compound of the formula (I) Wherein Ar is phenyl or an aromatic 5- or 6-membered C-bound heteroaromatic radical, wherein Ar may carry 1 radical R⁶ and wherein Ar may also carry I or 2 radicals R^b; X is N or CH; E is CR⁶R⁷ or NR³; R¹ is C₁-C₄-alkyl, C₃-C4-cycloalkyl, C₃-C₄-cycloalkylmethyl, C₃-C₄-alkenyl, fluorinated C₁-C₄-alkyl, fluorinated C₃-C₄-cycloalkyl, fluorinated C₃-C₄-cycloalkylmethyl, fluorinated C₃-C₄-alkenyl, formyl or C₁-C₃-alkylcarbonyl; R^1a is H or R^1a and R² or R^1a and R^2a together are (CH₂)_n with n being 1, 2, 3 or 4; R² and R^2a each independently are H, CH₃, CH₂F, CHF₂ or CF₃; R³ is H or C,-C4-alkyl; and the physiologically tolerated acid addition salts of these compounds. The invention also relates to pharmaceutical compositions comprising at least one compound of the formula (I) or a pharmaceutically acceptable salt thereof and to a method for treating a medical disorder susceptible to treatment with a dopamine D3 receptor ligand, said method comprising administering an effective amount of at least one compound of the formula (I) or a pharmaceutically acceptable salt thereof.