Oregon Health & Science University

State of Oregon

University of California

Duke University

Hoffmann-la Roche Inc.

Chinese Academy of Sciences

Olivier Civelli

David K Grandy

James R Bunzow

Rainer Reinscheid

Hans-Peter Nothacker

Hubert H Van Tol

Curtis A Machida

Hubert Henri-Marie Van Tol

Zhiwei Wang

Steven Lin

Qun Y Zhou

Marc G Caron

Yan Zhang

Frederick James Monsma, Jr

Xinmiao Liang

James Richard Martin

Chaoran Wang

Jean-Luc Moreau

Xiuli Zhang

Lien Wang

Yanling Xu

Frederick Monsma

Qun-Yong Zhou

Allen Dearry

Pierre Falardeau

Jay A Gingrich

Frederick James Monsma

Rainer Klaus Reinscheid

Yanxiong Ke

A method of treating nervous system diseases associated with dopamine receptors comprising administering a patent in need a compound having a structure of general formula (I) or a pharmaceutical acceptable salt, hydrate, or solvate thereof in a pharmaceutically effective amount, and a method of making the compound having the structure of general formula (I) or a pharmaceutical acceptable salt, hydrate, or solvate thereof. The compound of formula (I) has multiple pharmacological functions such as the functions of activating opioid receptors and blocking dopamine D2 receptors, and has good physicochemical properties and oral bioavailability. General animal experiments show that such a compound has significant and long-lasting analgesic and calming effects and can be used to treat pain and other mental illnesses.

Use and preparation method of berberine compounds

Compositions and methods that act on Neuropeptide S receptors (NPSR) (also known as 'TGR23' or 'vasopressin receptor-related receptor 1 (VRR1)') to cause desired effects in the bodies of human or animal subjects. Neuropeptide S (NPS) and other agonists of the NPSR may be administered to cause arousal, awakening, alertness, spontaneous movement, bronchoconstriction, contraction of bronchial smooth muscle or other effects. Antagonists of the NPSR may be administered to cause decreased arousal, decreased awakening, decreased alertness, decreased spontaneous movement, sleep, somnolence, sedation, anxiolytic effects, normalized sleep patterns, normalized sleep stages, increased duration of sleep, bronchodilation, relaxation of broncheal smooth muscle or other effects.

Therapies which act on neuropeptide S receptors

The present invention is directed toward antibodies, particularly monoclonal antibodies, which bind specifically to a novel human D4 dopamine receptor in sensitive and specific immunological assays useful for the detection, quantization, and characterization of human D4 dopamine and dopamine analogues.

Human dopamine receptor and its uses

The invention provides methods of screening for a compound for promoting wakefulness in a mammal. The method is practiced by providing a compound that is a PrRP receptor agonist and determining the ability of the compound to promote wakefulness. Also provided by the invention are methods of screening for a compound for promoting sleep in a mammal. The methods are practiced by providing a compound that is a PrRP receptor antagonist and determining the ability of the compound to promote sleep. In addition, the invention provides a method of promoting wakefulness in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor agonist. The invention further provides a method of promoting sleep in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor antagonist.

Screening and therapeutic methods for promoting wakefulness and sleep

The present invention provides an isolated nucleic acid molecule containing a nucleotide sequence which encodes an ADP-glucose receptor, and isolated polynucleotides therefrom. Also provided is an isolated ADP-glucose receptor polypeptide, an isolated immunogenic peptide therefrom, and antibodies specific therefor. The invention also provides a method of identifying an ADP-glucose receptor agonist or antagonist, by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detection of a G-protein coupled signal in response to ADP-glucose, and identifying a candidate compound that alters production of the signal. Further provided is a method of identifying an ADP-glucose receptor ligand, by contacting an ADP-glucose receptor with one or more candidate compounds under conditions suitable for detecting selective binding of ADP-glucose to ADP-glucose receptor, and identifying a candidate compound that selectively binds the ADP-glucose receptor. Also provided are methods of diagnosing or determining susceptibility to ADP-glucose receptor associated conditions, by detecting in a sample from the individual expression of ADP glucose receptor nucleic acid molecules or polypeptides.

Methods of identifying and ADP-glucose receptor ligand, agonist or antagonist

The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

Human dopamine receptor and uses

The present invention relates to a novel mammalian opioid receptor protein and ligands that bind to such proteins. The invention is directed toward the isolation, characterization and pharmacological use of an endogenous ligand that specifically binds to a novel mammalian opioid receptor protein heterologously expressed in mammalian cells. The invention specifically provides the isolated peptide ligand and analogues, derivatives and variants thereof. The invention specifically provides tyrosine substitution variants of the peptide ligand that specifically bind to the opioid receptor and can be radioiodinated. Also provided are methods of making such peptide ligands and methods of using the ligands for diagnostic and therapeutic uses and for the identification of other naturally-occurring or synthetic opioid receptor ligands.

Method of screening of a compound for binding to MSOR

The invention provides a substantially pure Prolactin Releasing Peptide (PrRP) functional analog which suppresses absence seizures in a mammal, and related pharmaceutical compositions. The invention also provides a method of controlling absence seizures in a mammal, by administering to a mammal susceptible to absence seizures an effective amount of PrRP or a PrRP functional analog. Also provided are methods of identifying a compound that modulates AMPA receptor signaling in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to modulate AMPA receptor signaling. The invention also provides methods of identifying a compound for controlling absence seizures in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to control absence seizures in a mammal. Also provided are pharmaceutical compositions for controlling absence seizures in a mammal. The compositions and related methods contain a compound identified by the methods of the invention as a compound that modulates AMPA receptor signaling or as a compound that controls absence seizures.

Methods of identifying compounds for controlling absence seizures in a mammal relating to prolactin-releasing peptide(PrRP)

A mammalian D dopamine receptor gene has been cloned. Thus, DNA sequences encoding all or a part of the dopamine receptor are provided, as well as the corresponding polypeptide sequences and methods for producing the same both synthetically and via expression of a corresponding sequence from a host transformed with a suitable vector carrying the corresponding DNA sequence. The various structural information provided by this invention enables the preparation of labeled or unlabeled immunospecific species, particularly antibodies, as well as nucleic acid probes labeled in conventional fashion. Pharmaceutical compositions and methods of using various products of this invention are also provided.

Dopamine receptors and genes

The present invention relates to a method of screening for a therapeutically useful compound which comprises testing an LC132 receptor agonist in a screening assay for psychiatric and/or neurological disorders. More particularly, the screening method is based on contacting an LC132 receptor with an agent suspected of being an agonist of the LC132 receptor function, followed by the detection of the binding and/or the agonist activity of the compound and then testing of an agent with LC132 agonist activity in an antiepileptic, anticonvulsant or anxiolytic screening assay.

Method of identifying compounds having antiepileptic anticonvulsant or anxiolytic activities

The present invention relates to a novel-mammalian methadone-specific opioid receptor protein and genes that encode such a protein. The invention is directed toward the isolation, characterization and pharmacological use of mammalian methadone-specific opioid receptor proteins. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to the rat homologue of the mammalian methadone-specific opioid receptor gene. Also provided are recombinant expression constructs capable of expressing the mammalian methadone-specific opioid receptor genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the mammalian methadone-specific opioid receptor proteins encoded therein. The invention also provides methods for screening compounds in vitro that are capable of binding to the mammalian methadone-specific opioid receptor proteins of the invention, and further characterizing the binding properties of such compounds in comparison with known opioid receptor agonists and antagonists.

Mammalian methadone-specific opioid receptor gene and uses

A mammalian D,dopamine receptor gene has been cloned. Thus, DNA sequences encoding all or a part of the dopamine receptor are provided, as well as the corresponding polypeptide sequences and methods for producing the same both synthetically and via expression of a corresponding sequence from a host transformed with a suitable vector carrying the corresponding DNA sequence. The various structural information provided by this invention enables the preparation of labeled or unlabeled immunospecific species, particularly antibodies, as well as nucleic acid probes labeled in conventional fashion. Pharmaceutical compositions and methods of using various products of this invention are also provided.

The present invention is directed toward isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

The present invention relates to a novel mammalian methadone-specific opioid receptor protein and genes that encode such a protein. The invention is directed toward the isolation, characterization and pharmacological use of mammalian methadone-specific opioid receptor proteins. The invention specifically provides isolated complementary DNA copies of mRNA corresponding to the rat homologue of the mammalian methadone-specific opioid receptor gene. Also provided are recombinant expression constructs capable of expressing the mammalian methadone-specific opioid receptor genes of the invention in cultures of transformed prokaryotic and eukaryotic cells, as well as such cultures of transformed cells that synthesize the mammalian methadone-specific opioid receptor proteins encoded therein. The invention also provides methods for screening compounds in vitro that are capable of binding to the mammalian methadone-specific opioid receptor proteins of the invention, and further characterizing the binding properties of such compounds in comparison with known opioid receptor agonists and antagonists.

Growing community of inventors

Irvine, CA, United States of America

Olivier Civelli