Autism (ASD) symptoms of aggression-toward others or self, and paranoia with social isolation, are presently treated with antipsychotic medications such as haloperidol, Thorazine, and newer generation antipsychotics risperidone and aripiprazole (latter two are the only FDA approved drugs for treating autism irritability/aggression). But these antipsychotics including the newer generation, after a two or more years of use, often lead to irreversible tardive dyskinesia, other dystonias, loss of effectiveness, and brain volume loss. The present invention overcomes the irreversible tardive dyskinesia and dystonias and loss of effectiveness with long term-use of antipsychotics, by replacing the antipsychotic completely with a three (3) drug novel composition consisting of fluoxetine or sertraline with guanfacine and oxcarbazepine. This novel composition markedly reduces aggression and paranoia/social isolation in ASD adults and adolescents without concomitant antipsychotic use that often causes irreversible tardive dyskinesia, eventual tachyphylaxis, or brain volume loss from antipsychotic long-term use.

Autism (ASD) symptoms of aggression-toward others or self, and paranoia with social isolation, are presently treated with antipsychotic medications such as haloperidol, Thorazine, and newer generation antipsychotics risperidone and aripiprazole (latter two are the only FDA approved drugs for treating autism irritability/aggression). But these antipsychotics including the newer generation, after a two or more years of use, often lead to irreversible tardive dyskinesia, other dystonias, loss of effectiveness, and brain volume loss. The present invention overcomes the irreversible tardive dyskinesia and dystonias and loss of effectiveness with long term-use of antipsychotics, by replacing the antipsychotic completely with a three (3) drug novel composition consisting of fluoxetine or sertraline with guanfacine and oxcarbazepine. This novel composition markedly reduces aggression and paranoia/social isolation in ASD adults and adolescents without concomitant antipsychotic use that often causes irreversible tardive dyskinesia, eventual tachyphylaxis, or brain volume loss from antipsychotic long-term use.

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

The invention utilizes virtual screening strategy to seek for current market drugs as anti-schizophrenia therapy drug repurposing. Drug repurposing strategy finds new uses other than the original medical indications of existing drugs. Finding new indications for such drugs will benefit patients who are in needs for a potential new therapy sooner since known drugs are usually with acceptable safety and pharmacokinetic profiles. In this study, repurposing marketed drugs for DAAO inhibitor as new schizophrenia therapy was performed with virtual screening on marketed drugs and its metabolites. The identified and available drugs and compounds were further confirmed with in vitro DAAO enzymatic inhibitory assay.

Disclosed herein are methods for treating juvenile onset neurological conditions, such as autism (ASD), intellectual disability, or epilepsy, with an inhibitor of N-methyl-D-aspartate receptor (NMDAR). The inhibitor may be NitroSynapsin or a derivative thereof.

Disclosed herein are methods for treating juvenile onset neurological conditions, such as autism (ASD), intellectual disability, or epilepsy, with an inhibitor of N-methyl-D-aspartate receptor (NMDAR). The inhibitor may be NitroSynapsin or a derivative thereof.

The present invention discloses an application of a β3 adrenergic receptor (ADRB3) as a marker for detecting a plurality of diseases, and an application of anti-human ADRB3 monoclonal antibody in diagnosing a disease and preparing a drug for treating the disease. The present invention finds through research that the ADRB3 is a key receptor in nerve-endocrine-immunoregulatory network, and an ADRB3-mediated signaling pathway regulates proliferation and differentiation of neutrophils, lymphocytes and tumor cells. Under normal circumstances, the ADRB3 maintains the non-specific immunocompetence and specific immunocompetence of an organism, and eliminates pathogenic microorganisms and aged organism tissues to play a role in protecting the organism and anti-aging. Under pathological conditions, excessive activation of the signaling pathway will cause systemic chronic inflammation, and destroy immune homeostasis. Therefore, the ADRB3 can be used as a diagnostic marker and a therapeutic target for a plurality of diseases. Anti-human ADRB3 antibody can specifically bond with the ADRB3, regulate the activity of the ADRB3, has the functions of resisting cancer, inflammation, poisoning, shock, allergy, viral infection, autoimmune disease, disease caused by regenerative dysfunction, autoimmune disease, cachexia, cardiovascular and cerebrovascular disease, neurodegenerative disease and aging, regulating autophagy, treating aging disease, etc., and has important medical value and research and application prospects.

The present invention discloses an application of a β3 adrenergic receptor (ADRB3) as a marker for detecting a plurality of diseases, and an application of anti-human ADRB3 monoclonal antibody in diagnosing a disease and preparing a drug for treating the disease. The present invention finds through research that the ADRB3 is a key receptor in nerve-endocrine-immunoregulatory network, and an ADRB3-mediated signaling pathway regulates proliferation and differentiation of neutrophils, lymphocytes and tumor cells. Under normal circumstances, the ADRB3 maintains the non-specific immunocompetence and specific immunocompetence of an organism, and eliminates pathogenic microorganisms and aged organism tissues to play a role in protecting the organism and anti-aging. Under pathological conditions, excessive activation of the signaling pathway will cause systemic chronic inflammation, and destroy immune homeostasis. Therefore, the ADRB3 can be used as a diagnostic marker and a therapeutic target for a plurality of diseases. Anti-human ADRB3 antibody can specifically bond with the ADRB3, regulate the activity of the ADRB3, has the functions of resisting cancer, inflammation, poisoning, shock, allergy, viral infection, autoimmune disease, disease caused by regenerative dysfunction, autoimmune disease, cachexia, cardiovascular and cerebrovascular disease, neurodegenerative disease and aging, regulating autophagy, treating aging disease, etc., and has important medical value and research and application prospects.

The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: X.sup.1, X.sup.2, R.sup.1, R.sup.2, m and n are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, Parkinson's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder. ##STR00001##

Provided herein are multicyclic compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are useful for the treatment, prevention, and/or management of various neurological disorders, including but not limited to, psychosis and schizophrenia.