47 results about "Dopamine transport" patented technology

One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

Provided are analogs of methylphenidate (“MPH”) that are useful for the treatment of drug addiction, attention deficit disorder, attention deficit hyperactivity disorder, and depression. The MPH analogs are extended duration compounds that bind to the dopamine transporter and the reuptake of dopamine in the afflicted individual's brain. Because of the extended duration of the MPH analogs, administration of the compounds is only required on a once or twice daily schedule.

One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

The present invention discloses the application of bakuchiol compound in preparing medicine for treating psychogenic diseases and neurogenic diseases. Extracorporeal experiment and animal experiment show that the bakuchiol compound can suppressing dopamine transport protein, noradrenalin transport protein and 5-hydroxy tryptamine transport protein selectively, and no influence on gamma-aminobutyric acid transport protein and L-glytamic acid transport protein, no cytotoxicity, and antidepressant effect higher than available antidepressant medicine amfebutamoe hydrochloride. Therefore, the bakuchiol compound has excellent marketability in preparing medicine for treating psychogenic diseases and neurogenic diseases.

The present invention encompasses compositions for the treatment of Parkinson's disease comprising a therapeutically effective amount of levodopa or a metabolic precursor thereof and at least one dopamine transport inhibitor in sufficient amount to decrease dopamine degradation, wherein the dopamine transport inhibitor is administered to avoid dyskinesia.

A method of diagnosing attention deficient-hyperactivity disorder (ADHD) in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where an elevated level of dopamine transporter in the patient is indicative of ADHD. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

The present invention discloses an application of flavone compound or its derivative in preparation of medicine for curing psychic disease and nervous disease. Said invention also discloses a medicine composition containing flavone compound or its derivative. Said invention also provides an excitant of dopamine transport protein firstly, and the tests show that the dopamine transport protein can be excited.

The invention belongs to the field of medicinal chemistry, and relates to flavonoid derivatives and application thereof in preparing a medicinal composition for treating diseases related with dopamine transport protein. The flavonoid derivatives of the invention have a structure of a formula (I). A biological evaluation result shows that a compound of the invention represents better activation function on the dopamine transport protein compared with the prior art, can adjust the transport of dopamine by promoting the transport function of the dopamine transport protein, maintain extracellular dopamine concentration balance, and can be prepared into dopamine transport protein agonist used for treating mental diseases and neurological diseases. R1 is selected from hydroxy, alkoxyl of C1 to C8, ester group of C1 to C8, glucoside and halogen; R2 is selected from hydrogen, C7-hydroxy, C7-alkoxyl, C7-ester and C7-halogen respectively; and R3 is selected from the hydrogen respectively, or contain one or a plurality of substituent groups on a benzene ring, wherein the substituent groups are selected from the hydroxy, alkoxyl, ester group, aryl (heteroaryl), the hydrogen and glycoside group respectively.

The present invention relates to tropane derivatives having particular use for the in vivo detection of dopamine transporters.These derivatives meet the formulain which R1 is I or Sn (R3)3, R2 is for example the methyl group, and X and Y are various substituents.The derivatives with X=CH3 and Y=H show strong specificity for the dopamine transporter compared with the serotonin transporter (74% inhibition when the transporter is previously saturated with GBR 12909).

A method of diagnosing Lewy Body Dementia in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where a lowered level of dopamine transporter in the patient is indicative of Lewy Body Dementia. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

Derivatives of Sydnonimine and its analogues, which bind selectively to dopamine transporter (DAT) proteins are useful for treating and delaying the progression of disorders and illnesses that are alleviated by inhibiting dopamine reuptake.

One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

A method of diagnosing attention deficient-hyperactivity disorder (ADHD) in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where an elevated level of dopamine transporter in the patient is indicative of ADHD. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter over the serotonin transporter with a ratio of 10 or more. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.

A system for treating addictions includes genetic testing to determine the presence of allelic variants of genes shown to be associated with impulsive / addictive behaviors and a tailored rehabilitation regimen of specific physical exercise, special diet and particular dietary supplements to optimize the way mood elevation is achieved in the patient. The system further includes individual and group counseling and initial oxygen therapy. The genetic testing assesses the presence of gene polymorphism in at least one of D2 dopamine receptor gene (DRD2), dopamine transporter gene (DAT1), dopamine beta-hydroxylase gene (DBH) and serotonin transporter (SERT) gene. The dietary supplements are tailored to stimulate production of neuromediators or neurotransmitters, depending upon the polymorphism determined. The exercises include static and dynamic routines also tailored to the results of the genetic testing. After completion of the inpatient portion of the system, further therapies include daily exercise and dietary supplement programs tailored for each polymorphism discovered.

One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

A method of diagnosing attention deficient-hyperactivity disorder (ADHD) in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where an elevated level of dopamine transporter in the patient is indicative of ADHD. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and / or prevent neurodegeneration, and / or confer neuroprotective effects The screening methods utilize recombinant C. elegans expressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.

The invention provides a class of DAT-5HT2 antagonists, packaged pharmaceuticals comprising such antagonists, and their uses in treating, or manufacturing medicaments for treating disease conditions, including a movement disorder, attention deficit disorder or attention-deficit hyperactivity disorder, anxiety, depression or psychotic disorder. Related business methods such as marketing the inhibitors to healthcare providers are also provided.

One aspect of the present invention relates to polypharmacophoric compounds. In certain embodiments, the polyphamacophore compounds comprise individual pharmacophore units selected from the group consisting of D-1 agonists, D-2 agonists, D-3 agonists, D-4 agonists, irreversible monoamine inhibitors, reversible monoamine inhibitors, monoamine transporter inhibitors, COMT inhibitors, MAO inhibitors, and dopamine transporter inhibitors. Moreover, the present invention also relates to combinatorial libraries of polypharmacophoric compounds. Another aspect of the present invention relates to the use of a polypharmacophoric compound in a method of treating a mammal in need thereof. For example, a polypharmacophoric compound of the present invention may be used in a method of treating a mammal afflicted with Alzheimer's Disease, Huntington's Disease, depression, attention deficit disorder, autism, obesity, or inflammation.

A method of diagnosing Lewy Body Dementia in a human patient by assessing the level of dopamine transporter in at least one region of the patient's central nervous system, where a lowered level of dopamine transporter in the patient is indicative of Lewy Body Dementia. In embodiments of the invention, assessment of dopamine transporter levels includes assessing binding of a dopamine transporter ligand to the dopamine transporters using PET or SPECT.

The invention is designed to provide lobeline applied for preparing medicine used for curing neuron apoptosis. The invention also relates to the applications of the lobeline for curing a CNS degenerative disease medicine. The lobeline up-regulates the concentration of synapse intermission DA by inhibiting the transport of DAT, so the apoptosis speed of a nerve cell can be stopped or retarded with little adverse effect. The lobeline is proved that the lobeline can protect dopaminergic neuron, so the invention provides the new medicine used for the clinical treatment of the CNS degenerative disease.

Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter over the serotonin transporter with a ratio of 10 or more. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.

Disclosed herein are a method and a kit using a novel marker associated with depression. The marker for depression includes one or more selected from a noradrenaline transporter and a dopamine transporter. The method for determining depression includes a step of examining an expression level of the marker for depression in a blood sample collected from a subject.

Provided are in vivo screening methods to detect and identify substances that affect neuronal viability, and / or prevent neurodegeneration, and / or confer neuroprotective effects. The screening methods utilize recombinant C. elegans expressing a detectable marker in neuronal sub-groups and the use of neurotoxins specific to specific neuronal cells. Also provided are methods for identifying modulators of neurotransmitter transporters such as the dopamine transporter. Therefore, the invention provides methods for identifying substances that can be used in the prevention and therapy of neurodegenerative diseases.

A diagnostic formulation is provided comprising a tropane having a radioactive concentration of at least 1.6 mCi / mL at least about 51 hours post creation. The diagnostic formulation optionally comprises a radiolabeled dopamine transporter (DAT) ligand useful in the diagnosis of Parkinson's disease (PS). One example of a radiolabeled dopamine transporter (DAT) ligand example is [123I]-2β-carbomethoxy-3β-(4-flurophenyl)-N-(3-iodo-E-allyl) nortropane.

One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

One aspect of the present invention relates to polypharmacophoric compounds. In certain embodiments, the polyphamacophore compounds comprise individual pharmacophore units selected from the group consisting of D-1 agonists, D-2 agonists, D-3 agonists, D-4 agonists, irreversible monoamine inhibitors, reversible monoamine inhibitors, monoamine transporter inhibitors, COMT inhibitors, MAO inhibitors, and dopamine transporter inhibitors. Moreover, the present invention also relates to combinatorial libraries of polypharmacophoric compounds. Another aspect of the present invention relates to the use of a polypharmacophoric compound in a method of treating a mammal in need thereof. For example, a polypharmacophoric compound of the present invention may be used in a method of treating a mammal afflicted with Alzheimer's Disease, Huntington's Disease, depression, attention deficit disorder, autism, obesity, or inflammation.

New tropane analogs that bind to monoamine transporters are described, particularly, 8-aza, 8carbo and 8-oxo tropanes having 6- or 7-hydroxyl or ketone substituents. The compounds of the present invention can be racemic, pure R-enantiomers, or pure S-enantiomers. Certain preferred compounds of the present invention have a high selectivity for the DAT versus the SERT. Also described are pharmaceutical therapeutic compositions comprising the compounds formulated in a pharmaceutically acceptable carrier and a method for inhibiting 5-hydroxy-tryptamine reuptake of a monoamine transporter by contacting the monoamine transporter with a 5-hydroxytryptamine reuptake inhibiting amount of a compound of the present invention. Preferred monoamine transporters for the practice of the present invention include the dopamine transporter, the serotonin transporter and the norepinephrine transporter.