Vanderbilt University

Pharmorx Therapeutics, Inc.

Robert M Kessler

David M Bear

Tomas De Paulis

Jeffrey A Clanton

Howard E Smith

Aaron Janowsky

Thomas E Conturo

Aaron Janowski

Thomas De Paulis

The present invention relates to improved compositions and methods for the treatment or prevention of various diseases, including forms of depression, including, for example, breakthrough depression and treatment-refractory depression, and other mood disorders, as well as Parkinson's disease, bipolar disorder, bipolar disorder, attention deficit disorder (ADHD), Restless Leg Syndrome (RLS), and obesity. In some embodiments, the compositions and methods comprise low dose naltrexone or related opioid antagonists.

Treatments for depression and other diseases with a low dose agent

Methods and compositions are provided for preventing or reversing loss of the therapeutic effect of a drug, where the loss is associated with the repeated administration of the drug to a patient. The method includes administering to the patient a dopamine receptor agonist or partial agonist or a drug that increases the extracellular level of dopamine by enhancing release of dopamine, decreasing the removal of dopamine from the extracellular space, enhancing the synthesis of dopamine within the brain, or decreasing metabolic degradation of dopamine; and also administering to the patient an opioid receptor antagonist in an ultra-low dose amount, wherein the ultra-low dose amount is effective to prevent or reverse loss of therapeutic effects associated with the repeated administration of the drug to the patient. The methods are useful for various treatments, including treating Parkinson's Disease, Restless Leg Syndrome, depression, schizophrenia, psychostimulant drug abuse, or attention deficit disorder.

Compositions and methods for minimizing or reversing agonist-induced desensitization

Novel, substituted benzamides in radioiodinated form are useful in radiopharmaceutical compositions in nuclear medicine as imaging agents to detect, visualize, and analyze the distribution and function of the dopamine D2 receptor in the mammalian brain. These compounds have a specific combination of lipophilicity and dopamine D2 receptor affinity required to attain a required image contrast. The iodinated benzamides identified by the above discovery can be made by reacting a trialkyltin substituted benzamide with an acid in the presence of radioactive iodine which, in turn, is generated by in situ oxidation of an appropriate iodide nuclide salt.

Radioiodinated benzamines and method of their use as radioimaging

Novel, substituted benzamides in radioiodinated form are useful in radiopharmaceutical compositions in nuclear medicine as imaging agents to detect, visualize, and analyze the distribution and function of the dopamine D-2 receptor in the mammalian brain. The substituted benzamides and their racemic mixtures or their optically resolved enantiomers can be made by reacting a trialyltin substituted benzamide with an acid in the presence of radioactive iodine, generated by in situ oxidation of an appropriate iodide nuclide salt.

Radioiodinated benzamines method of their use as radioimaging agents

A method of inversion spin echo magnetic resonance imaging includes providing a specimen positioned within a main magnetic field, a source of RF signals, a receiver for receiving signals emitted from the specimen responsive to the RF pulses and emitting responsive output signals, a computer for receiving the output signals from the receiver and establishing image information related thereto and a visual display for displaying images obtained from the image information. During an initial echo period, imposing three pulses on the main magnetic field with the first and third pulses having a first value and the second pulse having a second value which may be approximately double the first value, creating an echo with the second pulse and the third pulse converting this echo into negative longitudinal magnetization. After an inversion period during a second echo period imposing fourth and fifth RF pulses in the same sequence and generally of magnitude as the first and second pulses, respectively, creating a spin echo with the fifth pulse and response to said spin echo emitting output information from the receiver means to the computer with the computer establishing image information which is delivered to the visual display. The apparatus provides magnetic field generation apparatus to provide a main magnetic field on a specimen and RF signal generating apparatus for emitting pulsed RF signals in order to establish predetermined pulse sequences and magnitudes with the resultant receiver and computer serving to convert the same into image information for visual display.

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Nashville, TN, United States of America

Robert M Kessler