Provided are compounds that are inhibitors of both rho kinase and of a monoamine transporter (MAT) act to improve the disease state or condition. Further provided are compositions comprising the compounds. Further provided are methods for treating diseases or conditions, the methods comprising administering compounds according to the invention. One such disease may be glaucoma for which, among other beneficial effects, a marked reduction in intraocular pressure (IOP) may be achieved.

The present invention relates to a neuromodulation apparatus and methods of using the neuromodulation apparatus for treating bladder dysfunction.

A pharmaceutical formulation for applying as an external application to the surface of the human body, in which decrease of viscosity during long-term storage is suppressed, and which contains sofpironium bromide, a water-soluble polymer, and ethanol, has a pH of 5.2 or lower, and is a uniformly dispersed, and non-aqueous formulation or low water content formulation with a water content of 5% or lower.

The invention provides methods for producing soluble di-chain BoNT/A protein.

A morphinan derivative represented by the following general formula (I): ##STR00001##
wherein R.sup.1 represents hydrogen, C.sub.1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms, and the alkylene moiety has 1 to 5 carbon atoms, etc.; R.sup.2 represents heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S and at least one carbon atom as ring-constituting atoms, containing at least one set of adjacent ring-constituting atoms bound by a double bond, and further substituted with at least one oxo group; Y binds to a carbon atom as a ring-constituting atom of R.sup.2; R.sup.3, R.sup.4, and R.sup.5 represent hydrogen, hydroxy, etc.; R.sup.6a and R.sup.6b represent hydrogen, etc.; R.sup.7 and R.sup.8 represent hydrogen, etc.; R.sup.9 and R.sup.10, which are the same or different, represent hydrogen, etc.; X represents O or CH.sub.2; and Y represents C(═O)); a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic drug, antidepressant, etc.

A morphinan derivative represented by the following general formula (I): ##STR00001##
wherein R.sup.1 represents hydrogen, C.sub.1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms, and the alkylene moiety has 1 to 5 carbon atoms, etc.; R.sup.2 represents heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S and at least one carbon atom as ring-constituting atoms, containing at least one set of adjacent ring-constituting atoms bound by a double bond, and further substituted with at least one oxo group; Y binds to a carbon atom as a ring-constituting atom of R.sup.2; R.sup.3, R.sup.4, and R.sup.5 represent hydrogen, hydroxy, etc.; R.sup.6a and R.sup.6b represent hydrogen, etc.; R.sup.7 and R.sup.8 represent hydrogen, etc.; R.sup.9 and R.sup.10, which are the same or different, represent hydrogen, etc.; X represents O or CH.sub.2; and Y represents C(═O)); a tautomer or stereoisomer of the compound, or a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic drug, antidepressant, etc.

The present invention provides a method and a pharmaceutical composition for the treatment of the NDO comprising the viral expression vector carrying a transcription cassette that harbors transgene(s) inhibiting/silencing neurotransmission or synaptic transmission of afferent neurons.

An article of manufacture according to the present invention comprises a composition including a glycosaminoglycan, a local anesthetic, and a buffer packaged in a syringe or vial constructed from either glass or a plastic selected from the group consisting of cyclic olefin polymer, cyclic olefin copolymer, or high density non-nucleated polypropylene. The composition has unexpectedly improved stability on storage. The composition can be formulated for treatment of a urinary tract disease or condition, such as interstitial cystitis, also known as bladder pain syndrome or hypersensitive bladder syndrome.

An article of manufacture according to the present invention comprises a composition including a glycosaminoglycan, a local anesthetic, and a buffer packaged in a syringe or vial constructed from either glass or a plastic selected from the group consisting of cyclic olefin polymer, cyclic olefin copolymer, or high density non-nucleated polypropylene. The composition has unexpectedly improved stability on storage. The composition can be formulated for treatment of a urinary tract disease or condition, such as interstitial cystitis, also known as bladder pain syndrome or hypersensitive bladder syndrome.

The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.