Abstract: The present disclosure relates to a more effective therapeutic agent capable of improving and treating the axial symptoms (particularly freezing of gait symptom) of patients with Parkinson's disease. Such symptoms in patients with Parkinson's disease can be improved and treated by using L-threo-3,4-dihydroxy-phenylserine (DOPS) and a COMT inhibitor in combination together, optionally with an L-DOPA preparation as well. As a result, the axial symptoms difficult to improve with conventional L-DOPA preparations can be treated, and a therapeutic agent and a treatment method are provided for the axial symptoms of patients with Parkinson's disease, particularly those suffering from the disease at a moderate level or higher.

Abstract: The present invention provides combinations of active agents, such combinations comprising one or more antifolate compounds. The particularly can include methotrexate and one or more further antifolate compounds. In specific embodiments, the combinations are useful for treating certain conditions, such as rheumatoid arthritis. The invention also provides articles useful to provide the combinations in desirable dosage forms and combinations. The combinations further may be useful in the treatment of further conditions, including abnormal cell proliferation, inflammatory diseases, asthma, and arthritis.

Abstract: The present invention provides combinations of active agents, such combinations comprising one or more antifolate compounds. The particularly can include methotrexate and one or more further antifolate compounds. In specific embodiments, the combinations are useful for treating certain conditions, such as rheumatoid arthritis. The invention also provides articles useful to provide the combinations in desirable dosage forms and combinations. The combinations further may be useful in the treatment of further conditions, including abnormal cell proliferation, inflammatory diseases, asthma, and arthritis.

Abstract: The present application relates to a novel method of preparing L-threo-dihydroxyphenylserine (droxidopa). Specifically, the application is directed to a method of preparing droxidopa via a deprotection step that is an alternative to deprotection steps that have been previously disclosed. The new deprotection strategy is advantageous in that it avoids the need to use hydrogenolysis or hydrazine.

Abstract: The present invention relates to pharmaceutical formulations for the controlled delivery of threo-3-(3,4-dihydroxyphenyl)serine (threo-DOPS) and derivatives of it. Such formulations can contain an extended or slow release component that maintains therapeutic concentration of threo-DOPS in the blood plasma over a prolonged time period. They can be further combined with an immediate release formulation to produce a product that, when administered to a patient in need thereof, results in substantially steady levels of active drug, eliminating the sharp peaks and troughs in blood plasma drug levels experienced with the existing threo-DOPS formulations.

Abstract: The present invention is directed to compounds that are specifically structured to provide enzyme inhibition. In specific embodiments, the enzyme inhibiting compounds exhibit antifolate activity. Particularly, the inventive compounds are formed of an antifolate residue that is active in inhibiting one or more of TS, DHFR, GAR, FPGS, and AICAR Tfase. The enzyme inhibiting compounds are useful in a variety of methods of treatment, including treating abnormal cell proliferation and treating inflammation.

Abstract: The present invention provides methods and systems for reducing falls in patients that are recurrent fallers. Specifically, the compositions, systems, and methods can relate to Parkinson's disease patients, particularly such patients that are suffering from neurogenic orthostatic hypotension. The compositions, systems, and methods comprise the use of droxidopa, optionally in combination with a further active agent. Administration of droxidopa has been found to reduce the mean number of falls per patient per week, as well as provide improvements in the patient's Hoehn and Yahr rating scale score, which is indicative of improvements in postural stability, and provide improvements in the patient's Unified Parkinson's disease Rating Scale score, which is indicative of improvements in the severity of motor and/or non-motor symptoms of Parkinson's disease.

Abstract: The present invention relates to pharmaceutical formulations for the controlled delivery of threo-3-(3,4-dihydroxyphenyl)serine (threo-DOPS) and derivatives of it. Such formulations can contain an extended or slow release component that maintains therapeutic concentration of threo-DOPS in the blood plasma over a prolonged time period. They can be further combined with an immediate release formulation to produce a product that, when administered to a patient in need thereof, results in substantially steady levels of active drug, eliminating the sharp peaks and troughs in blood plasma drug levels experienced with the existing threo-DOPS formulations.

Abstract: Compounds of formula (I) are provided, wherein X is CH?CH, CH2O wherein the oxygen atom is bound to ring B, or OCH2 wherein the oxygen atom is bound to ring A; Y is hydrogen, straight or branched C1-C6 alkyl or a pharmaceutically acceptable inorganic cation; R1 is ethyl or cyclopropyl; and R2 and R3 are the same or different and are selected from F, Cl, Br, CF3 and OCF3. The compounds are useful for the treatment of autoimmune diseases, inflammatory diseases, organ transplant rejection, and malignant neoplasia. Pharmaceutical compositions containing the compounds, methods of using the compounds, and methods for preparing the compounds are also provided.

Abstract: The present invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, for the treatment of conditions, such as mood disorders, sleep disorders, or attention deficit disorders. In certain embodiments, the compositions useful in the methods of the invention comprise droxidopa and a compound selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibiting compounds, cholinesterase inhibiting compounds, monoamine oxidase inhibiting compounds, norepinephrine reuptake inhibiting compounds, selective serotonin reuptake inhibiting compounds, tricyclic antidepressant compounds, serotonin norepinephrine reuptake inhibiting compounds, norepinephrine dopamine reuptake inhibiting compound, noradrenergic and specific serotonergic antidepressants, and combinations thereof.

Abstract: The present invention is directed to methods of treating neurally mediated hypotension. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, that can be administered to a patient for the treatment of neurally mediated hypotension.

Abstract: The present invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, for the treatment of conditions, such as mood disorders, sleep disorders, or attention deficit disorders. In certain embodiments, the compositions useful in the methods of the invention comprise droxidopa and a compound selected from the group consisting of DOPA decarboxylase inhibiting compounds, catechol-O-methyltransferase inhibiting compounds, cholinesterase inhibiting compounds, monoamine oxidase inhibiting compounds, norepinephrine reuptake inhibiting compounds, selective serotonin reuptake inhibiting compounds, tricyclic antidepressant compounds, serotonin norepinephrine reuptake inhibiting compounds, norepinephrine dopamine reuptake inhibiting compound, noradrenergic and specific serotonergic antidepressants, and combinations thereof.

Abstract: Compounds of formula (I) are provided, wherein X is CH?CH, CH2O wherein the oxygen atom is bound to ring B, or OCH2 wherein the oxygen atom is bound to ring A; Y is hydrogen, straight or branched C1-C6 alkyl or a pharmaceutically acceptable inorganic cation; R1 is ethyl or cyclopropyl; and R2 and R3 are the same or different and are selected from F, Cl, Br, CF3 and OCF3. The compounds are useful for the treatment of autoimmune diseases, inflammatory diseases, organ transplant rejection, and malignant neoplasia. Pharmaceutical compositions comprising the compounds, methods of using the compounds, and methods for preparing the compounds are also provided.

Abstract: The present invention relates to pharmaceutical formulations for the controlled delivery of threo-3-(3,4-dihydroxyphenyl)serine (threo-DOPS) and derivatives of it. Such formulations can contain an extended or slow release component that maintains therapeutic concentration of threo-DOPS in the blood plasma over a prolonged time period. They can be further combined with an immediate release formulation to produce a product that, when administered to a patient in need thereof, results in substantially steady levels of active drug, eliminating the sharp peaks and troughs in blood plasma drug levels experienced with the existing threo-DOPS formulations.

Abstract: The present invention provides methods of treating fibromyalgia or other diseases or conditions causing widespread pain and/or fatigue. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active agents, that can be used in the inventive methods. The methods of treatment can comprise treating, preventing, reducing, or eliminating a variety of symptoms recognized as indicative of fibromyalgia, such as chronic pain, allodynia, hyperalgesia, fatigue, sleep disturbance, and depression.

Abstract: The present invention is directed to antifolate compounds having the structure wherein: X is CHR9 or NR9; Y1, Y2, and Y3 independently are O or S; V1 and V2 independently are O, S, or NZ; Z is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl; R1 and R2 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, or alkaryl; R3 is H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, hydroxyl, or halo; and R4, R5, R6, R7, R8, and R9 independently are H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, acyl, —C(O)-alkyl, —C(O)-alkenyl, or —C(O)—alkynyl; as well as pharmaceutically acceptable esters, amides, salts, solvates, and prodrugs thereof.

Abstract: The present invention provides compositions and methods for the treatment of disorders of abnormal cell proliferation and/or inflammation, such as psoriasis and inflammatory bowel disease, in a human or other host animals.