The present invention relates to a compound represented by the general formula (I) (wherein the definition of each group has the same meaning as described in the specification). The compound is useful as preventive and/or therapeutic agent for KCNQ2-5 channel-related diseases.

##STR00001##

Unsaturated nitrogen heterocyclic compounds of formula (I): ##STR00001##
as defined in the specification, compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, Huntington's Disease, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

The invention provides methods and compositions for use of desmopressin in combination with an alpha-adrenergic receptor antagonist. The methods and compositions are useful in the treatment of nocturia and other urinary frequency disorders.

The invention relates to a liquid formulation comprising propylene glycol and an effective amount of an inodilator, an angiotensin converting enzyme inhibitor, or a combination of an inodilator and an angiotensin converting enzyme inhibitor and to use of the formulation for treating cardiac disease and/or hypertension.

Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is “turned on” only under such conditions.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.

A single-chain insulin analogue containing (i) diverse amino-acid substitutions at position A14; (ii) wild-type or variant residues at positions A8 and A14; and (ii) an engineered C-domain segment of lengths 4-6 containing a specific set of Alanine substitutions and/or deletions derived from the prototype C-domain sequence Glu-Glu-Gly-Pro-Arg-Arg. The analogue may otherwise be an analogue of a mammalian insulin, such as human insulin, may optionally include standard or non-standard modifications that (i) augment the stability of insulin, (ii) cause a shift in the isoelectric point to enhance or impair the solubility of the protein at neutral pH or (iii) reduce cross-binding of the protein to the Type I IGF receptor. Formulations of the above analogues at successive strengths U-100 to U-1000 in soluble solutions under acidic or neutral pH values (e.g., pH 3.0-4.2 and 6.5-7.8, respectively) and optionally in the presence of zinc ions at a molar ratio of 2.2-10 zinc ions per six insulin analogue monomers. A method of treating a patient with diabetes mellitus comprising the administration of a physiologically effective amount of the protein or a physiologically acceptable salt thereof to a patient. Use of a single-chain insulin analogue of the present invention in an insulin delivery device (such as a pump or pen) is envisioned.

[Problem] The purpose of the present invention is to provide a novel technique associated with anti-obesity improvement.

[Solution] The present invention relates to an anti-obesity agent comprising lactononadecapeptide (LNDP, Asn-Ile-Pro-Pro-Leu-Thr-Gln-Thr-Pro-Val-Val-Val-Pro-Pro-Phe-Leu-Gln-Pro-Glu) or a salt thereof. The present invention also relates to a pollakiuria improving agent and an autonomic nerve activity regulator each comprising LNDP.

There is provided a pharmaceutical composition which includes, as an active ingredient, a combination drug formulation of potassium citrate and sodium citrate hydrate or a sodium bicarbonate formulation. The prevention or treatment of nocturnal polyuria is achieved by administering the pharmaceutical composition.