Abstract: The present invention provides for compounds of Formula (I) wherein A, L, W, and R1 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of CLL, SLL, and/or ALL.

Abstract: In the present disclosure, doxycycline-inducible astrocyte-specific HIV Tat transgenic mice (iTat), a surrogate HAND model, were treated with PNU-125096, a positive allosteric modulator of ?7 nicotinic acetylcholine receptor (?7 nAChR) and effects on Tat-induced behavioral impairments and neuropathologies were observed. This disclosure shows that PNU-125096 treatment significantly improved locomotor, learning and memory deficits of iTat mice while inhibited glial activation and increased PSD-95 expression in the cortex and hippocampus of iTat mice. ?7 nAChR knockout eliminated the protective effects of PNU-125096 on iTat mice. In addition, inhibition of p38 phosphorylation by SB239063, a p38 MAPK-specific inhibitor, exacerbated Tat neurotoxicity in iTat mice. These findings demonstrated for the first time that ?7 nAChR activation led to protection against HAND and suggest that ?7 nAChR and PNU-125096 hold significant promise for development of therapeutics for HAND.

Abstract: Disclosed herein are new dosage regimens for deuterium-substituted benzoquinoline compounds, and methods for the treatment of abnormal muscular activity, movement disorders, and related conditions.

Abstract: A method of predicting a mood state of a user may include recording an audio sample via a microphone of a mobile computing device of the user based on the occurrence of an event, extracting a set of acoustic features from the audio sample, generating one or more emotion values by analyzing the set of acoustic features using a trained machine learning model, and determining the mood state of the user, based on the one or more emotion values. In some embodiments, the audio sample may be ambient audio recorded periodically, and/or call data of the user recorded during clinical calls or personal calls.

Abstract: A opioid taper regimen, and its method of manufacture, for use in a method of opioid reduction leading to abstinence. Said regimen is administered within the range of 2 to 4 years, or more. The regimen comprises novel approaches to common problems encountered during tapers of low dose opioid addiction. The reduction regimen is generally linear; reduces the dosage level once per week; doses every six hours; reduces doses by steps in the range of about 0.001 to 0.0500 mg; has, near the end, ten weeks of doses of about 0.0025 mg buprenorphine q.i.d.; followed by four or more weeks of placebos. Instructions for manufacture of doses that differ by 0.0025 mg and 0.0050 mg buprenorphine are specified.

Abstract: The present disclosure relates to compounds of Formula (I) and (II): and to their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for modulating H1 and 5-HT2A receptors and are to be used in the treatment of sleep disorders, such as sleep fragmentation, disturbed sleep/arousals, and arousal threshold.

Abstract: A method for diagnosing Alzheimer's disease (AD) includes: obtaining a blood sample from a human subject suspected of having AD; determining a G72 protein level in the blood sample; determining an SLC7A11 mRNA expression level in the blood sample; comparing the G72 protein level with a first predetermined standard; comparing the SLC7A11 mRNA expression level with a second predetermined standard; and diagnosing the human subject with AD when the G72 protein level is higher than the first predetermined standard and the SLC7A11 mRNA expression level is higher than the second predetermined standard. An effective amount of a pharmaceutical composition may be administered to the diagnosed human subject for treating AD.

Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof.

Abstract: Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.

Abstract: Tricyclic dibenzothiazepine compounds for use in the treatment of respiratory depression.

Abstract: Disclosed are compositions and methods for the treatment of a subject having an autism spectrum disorder. The disclosed compositions may contain racemic ketamine or S-ketamine. The disclosed methods of administering the compositions include intranasal administration to a subject having an autism spectrum disorder.

Abstract: Provided herein are methods of diagnosing depressive disorders in a subject by comparing a CDP-diacylglycerol synthase 1 enzyme activity or expression level to enzyme activity or expression level of CDP-diacylglycerol synthase 1 in a control subject. Also herein are methods of predicting therapeutic efficacy of an antidepressant drug in a subject with depressive disorders by monitoring enzyme activity or expression level of CDP-diacylglycerol synthase 1 in the subject. Further provided herein are methods of identifying a compound effective to treat or alleviate the symptoms of depression by monitoring enzyme activity or expression level of CDP-diacylglycerol synthase 1 in a tissue. Further provided are kits for diagnosing depressive disorders.

Abstract: The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating fatty acids to quetiapine. Pharmaceutical compositions and methods of synthesizing conjugates of the present technology are also provided. Methods of treating patients with the compositions of the present technology are also provided.

Abstract: This invention relates to a method for combating adverse effects arising from antipsychotic treatment. The invention furthermore relates to novel pharmaceutical compositions comprising a therapeutically effective combination of a compound of formula I and an antipsychotic drug.

Abstract: The invention relates to compounds of Formula I, wherein R1, R2, and R3 are defined in the specification, useful for the synthesis of novel conjugates and immunogens derived from quetiapine. The invention also relates to conjugates of a quetiapine hapten and a protein.

Abstract: A method of treating an individual having Down syndrome or Alzheimer's disease, which entails the step of administering an amount of one or more compounds to the individual which improve cognitive functioning in the individual by increasing hippocampal NE levels.

Abstract: Tricyclic dibenzothiazepine compounds for use in the treatment of respiratory depression.

Abstract: Described are oral dosage forms that contain abuse-deterrent features and that contain core-shell polymers that include an active pharmaceutical ingredient, with particular examples including immediate release dosage forms that contain a drug that is commonly susceptible to abuse.

Abstract: Embodiments disclosed herein generally relate to acamprosate formulations, methods of use of the formulations, to methods of using the formulations in combination with at least one other medication, and to combination products and compositions comprising the formulations and at least one other medication, such as neuroleptic (antipsychotic) and/or antidepressant drugs.

Abstract: Described are oral dosage forms that contain abuse-deterrent features and that contain core-shell polymers that include an active pharmaceutical ingredient, with particular examples including immediate release dosage forms that contain a drug that is commonly susceptible to abuse.

Abstract: Described are oral dosage forms that contain abuse-deterrent features and that contain core-shell polymers that include an active pharmaceutical ingredient, with particular examples including immediate release dosage forms that contain a drug that is commonly susceptible to abuse.

Abstract: Described are immediate release oral dosage forms that contain abuse-deterrent features. In particular, the disclosed dosage forms provide deterrence of abuse by ingestion of multiple individual doses. In addition, the disclosed dosage forms provide protection from overdose in the event of accidental or intentional ingestion of multiple individual doses.

Abstract: Disclosed herein are compositions and methods for treating a psychiatric disorder or symptoms thereof in a patient. The compositions comprise a compound that modulates KCNQ (Kv7) potassium channel activity and the methods include administering an effective amount of the compound that modulates KCNQ (Kv7) potassium channel activity.

Abstract: The present invention relates to a gastric retentive tablet composition comprising: (1) coated particles essentially consisting of a drug and an amino methacrylate copolymer, (2) a methacrylic acid copolymer and (3) an excipient, wherein items 1, 2, and 3 are blended together, and then compressed into a gastric retentive tablet. Thus, the coated particles (item 1), a methacrylic acid copolymer and the excipient are evenly distributed in the tablet. The excipient is selected from a group consisting of a retarding agent, a binder, a filler, a chelating agent, a diluent, a disintegrant, a lubricant, a colorant, a solubilizing agent, or a mixture thereof. The coated particles (item 1) do not contain methacrylic acid polymer.

Abstract: This disclosure relates to compounds for the inhibition of histone deacetylase and treatment of a cognitive disorder or deficit. More particularly, the disclosure provides for compounds of formula (I) wherein (I), Q, J, L and Z are as defined in the specification.

Abstract: Use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals for the treatment of agitation, aggressive behaviors, posttraumatic stress disorder or impulse control disorders.

Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein -D is an amine containing biologically active moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I): wherein the dashed line indicates the attachment to the amine of the biologically active moiety and wherein R1, R1a, R2, R2a, R3, R3a, X, X1, X2, X3 have the meaning as indicated in the description and the claims and wherein L1 is substituted with one to four groups L2-Z and optionally further substituted, provided that the hydrogen marked with the asterisk in formula (I) is not replaced by a substituent; wherein L2 is a single chemical bond or a spacer; and Z is a carrier group. The invention also relates to A-L, wherein A is a leaving group, pharmaceutical composition comprising said prodrugs and their use as medicaments.

Abstract: The present disclosure relates to compounds that are sodium channel inhibitors and to their use in the treatment of various disease states, including cardiovascular diseases and diabetes. In particular embodiments, the structure of the compounds is given by Formula I: wherein Y, Z, n, R1 and R3 are as described herein, to methods for the preparation and use of the compounds and to pharmaceutical compositions containing the same.

Abstract: Alcoholism, and symptoms and negative effects thereof may be treated using ibudilast or a pharmaceutically acceptable salt thereof. Abstinence from alcohol consumption may be maintained using ibudilast or a pharmaceutically acceptable salt thereof. Withdrawal from alcohol may be facilitated and negative effects thereof reduced by using ibudilast or a pharmaceutically acceptable salt thereof.

Abstract: The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating fatty acids to quetiapine. Pharmaceutical compositions and methods of synthesizing conjugates of the present technology are also provided. Methods of treating patients with the compositions of the present technology are also provided.

Abstract: Monomeric and dimeric trioxane thioacetals and methods of their use for treating subjects infected with malaria or other parasitic infectious diseases including, but not limited to, toxoplasmic infection; subjects afflicted with psychiatric conditions associated with toxoplasmic infection; and subjects afflicted with cancer.

Abstract: The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1 and R2 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

Abstract: The present invention relates to the detection of markers in exhaled breath, wherein the detection of the presence or absence of the marker(s) in exhaled breath is used to assess various clinical data, including patient adherence in taking the medication and patient enzymatic (metabolic) competence in metabolizing the medication. An embodiment of the invention comprises a parent therapeutic agent labeled with a marker, where upon metabolism (e.g., via enzymatic action) of the therapeutic agent, the marker becomes volatile or semi-volatile and is present in the breath. In certain related embodiments, the marker contain a deuterium label, which is also present in the breath upon metabolism of the therapeutic agent. In another embodiment of the invention, the therapeutic agent is associated with a taggant (that may be either labeled or unlabeled with deuterium), which in turn will generate a marker in the breath that is easily measurable.

Abstract: The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating fatty acids to quetiapine. Pharmaceutical compositions and methods of synthesizing conjugates of the present technology are also provided. Methods of treating patients with the compositions of the present technology are also provided.

Abstract: This document provides methods and materials related to genetic markers for predicting response to a treatment for schizophrenia (SZ). For example, methods for using such genetic markers to select optimal treatments are provided.

Abstract: The present invention relates to the discovery of a novel opioid modulator effective in reducing pharmacologically induced weight gain associated with atypical antipsychotic use. The present invention provides methods of reducing antipsychotic induced weight gain, methods for suppressing food intake and reducing ghrelin levels induced by atypical antipsychotic medications in a patient.

Abstract: This invention pertains to a multi-layered tablet for a triple combination release of active agents to an environment of use. More particularly, the invention pertains to a multi-layered tablet (1) comprising two external drug-containing layers (2 and 3) in stacked arrangement with respect to and on opposite sides of an oral dosage form (4) that provides a triple combination release of at least one active agent. In one embodiment of the invention the dosage form is an osmotic device. In another embodiment of the invention the dosage form is a gastro-resistant coated core. In yet another embodiment of the invention the dosage form is a matrix tablet. In a different embodiment the dosage form is a hard capsule.

Abstract: This invention relates to genetic markers of mental illness, e.g., schizophrenia (SZ), and methods of use thereof.

Abstract: Provided is a method for diagnosis of schizophrenia, which comprises: detecting G72 gene product in a body fluid sample from a subject by an assay to determine G72 expression level; comparing said G72 expression level to a baseline G72 expression; and relating the G72 expression level to the patient's risk of schizophrenia by assigning an increased risk of schizophrenia when said G72 expression level is greater than said baseline G72 expression. Through detecting G72 expression level in a peripheral sample, the method can be simply performed by an in vitro assay and accurately predict or diagnose a subject with schizophrenia.

Abstract: The presently described technology provides a novel class of prodrugs of quetiapine that can be synthesized by chemically conjugating amino acids to quetiapine. The present technology also provides methods of treating patients, pharmaceutical compositions and methods of synthesizing conjugates of the present technology.

Abstract: The present invention is directed to CNS pharmaceutical compositions and methods of use. The pharmaceutical compositions comprise a CNS active agent and preferably at least two vagal neuromodulators, one of which is a mechanoreceptor stimulator. The vagal neuromodulators are preferably in an amount sufficient to reduce a somnolence side-effect of the CNS active agent without changing its therapeutic efficacy/activity. The invention further encompasses a method of reducing CNS active agent side-effects. The method typically comprises oral administration of at least one CNS active agent to a patient at the conventionally accepted dose; and administration of at least two vagal neuromodulators to the patient so that at least one neuromodulator is administered or released from dosage form after the CNS active agent is administered and/or released.

Abstract: A compound of formula I: or a pharmaceutically or veterinarily acceptable salt thereof, or a pharmaceutically or veterinarily acceptable solvate of either entity, wherein: R1, R2, R3, R4, R5, R6, X and m are as defined herein.

Abstract: Novel 5-HT3 receptor modulators are disclosed. These compounds are used in the treatment of various disorders, including chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, and irritable bowel syndrome. Methods of making these compounds are also described in the present invention.

Abstract: The invention relates to methods and compositions for treating schizophrenia or bipolar disorder (in particular, mania) by using a combination of a synaptic vesicle protein 2A (SV2A) inhibitor and an antipsychotic or their pharmaceutically acceptable salts, hydrates, solvates, polymorphs thereof. In some embodiments, the methods and the compositions are for treating one or more positive and/or negative symptoms, as well as cognitive impairment, associated with schizophrenia or bipolar disorder (in particular, mania).

Abstract: The present invention relates to 4-((1R,3S)-6-chloro-3-phenyl-indan-1yl)-1,2,2-trimethyl-piperazine and the salts thereof with activity at dopamine D1 and D2 receptors as well as the serotonin 5HT2 receptor for the treatment of diseases in the central nervous system in a once weekly dosing regime.

Abstract: The present invention relates to the C-13 molecule (methyl 2-{5-[(3-benzyl-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene)methyl]-2-furyl}-benzoate) and to organic molecules functionally equivalent to the C-13 molecule, capable of inhibiting the binding of an antibody or antibody fragment with the human Syk protein tyrosine kinase, to the use of these molecules for the production of medicaments for the prevention or treatment of diseases dependent on metabolic pathways involving Syk, and also to a method for identifying such molecules.

Abstract: The present invention relates to new cyclohexyl urea modulators of D2 receptors and/or modulators of D3 receptors, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: Provided is a method for diagnosis of schizophrenia, which comprises: detecting G72 gene product in a body fluid sample from a subject by an assay to determine G72 expression level; comparing said G72 expression level to a baseline G72 expression; and relating the G72 expression level to the patient's risk of schizophrenia by assigning an increased risk of schizophrenia when said G72 expression level is greater than said baseline G72 expression. Through detecting G72 expression level in a peripheral sample, the method can be simply performed by an in vitro assay and accurately predict or diagnose a subject with schizophrenia.

Abstract: The present invention includes methods for treating sun-exposed skin, such as treating photoaging and treating skin cancer. Also included are methods for altering a cell's response to ultraviolet radiation. The methods include administration of quetiapine or an analog thereof or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

Abstract: A sleep composition including zolpidem and quetiapine in combination provides a healthy sleep pattern allowing the user to get seven or eight hours sleep. The amount of each ingredient in the combination is lower than the amount usually needed to provide this amount of sleep when the ingredients are being used alone.