Dopamine D3 Receptor Agonist Compounds, Methods of Preparation, Intermediates Thereof, and their Methods of Use
Due to the large degree of homology among dopamine D2-like receptors, discovering ligands capable of discriminating between the D2, D3, and D4 receptor subtypes remains a significant challenge. The development of subtype-selective pharmaceutical small molecules to activate (agonists) signals regulated by D2-like receptors has been especially difficult.
Big data usually means big sample size with many outliers, in which traditional scalable L2-norm principal component analysis (L2-PCA) will fail. Current existing L1-norm PCA (L1-PCA) methods can improve robustness over outliers, however, its scalability is usually limited in either sample size or dimension size. The inventor proposes an online flipping method to solve L1-PCA challenges, which is not only convergent asymptotically (or with big data), but also achieves most efficiency in the sense each sample is visited only once to extract one principal component (PC).
There are no analgesics to ameliorate chronic pain without adverse side-effects (e.g., respiratory depression, gastrointestinal effects, tolerance, dependence), thus forcing patients into a difficult choice of negative impacts on quality of life. Most of the analgesics used for chronic and acute pain are drugs such as oxycodone, morphine, oxymorphone, and codeine. All of these opioids have been subject to misuse; prescription drug abuse is a severe problem worldwide, causing high mortality and greatly increased emergency room visits.
Researchers at the National Institute on Drug Abuse (NIDA) have developed software that provides personalized feedback for treating drug dependence, alcoholism, smoking cessation, pain management, and associated risky behaviors. The tool is designed for both healthcare providers at the point-of-care and for self-help. Many people who could benefit from treatment do not receive it because of its low availability and high cost.
The National Institute on Drug Abuse (NIDA), Biomedical Informatics section, developed the Mobile Interconnected Evaluation & Learning (MIEL) as a mobile health application. MIEL is used for real-time communication of patient-reported assessment data associated with automatically collected geolocation data on one side and the user’s enterprise-scale patient record system on the other.
Dopamine is a major neurotransmitter in the central nervous system and among other functions is directly related to the rewarding effects of drugs of abuse. Dopamine signaling is mediated by D1, D2, D3, D4 and D5 receptors. The dopamine D3 receptor is a known target to treat a variety of neuropsychiatric disorders, including substance use disorders (e.g. cocaine and opioid), schizophrenia and depression.
The available system is the Human Research Information System (HuRIS), an integrated advanced clinical/research informatics series of systems—that is, an intelligent electronic environment for the collection, organization and retrieval of information in clinical/scientific decision support—which enables data and resource sharing in real time among authorized users at our clinics. (Individual systems or subsystems may be licensable.)
Researchers at the National Institute on Drug Abuse developed a mobile health technology to monitor and predict a user’s psychological status and to deliver an automated intervention when needed. The technology uses smartphones to monitor the user’s location and ask questions about psychological status throughout the day. Continuously-collected ambulatory psychological data are fused with data on location and responses to questions. The mobile data are combined with geospatial risk maps to quantify exposure to risk and predict a futu
Dopamine and its receptors play a critical role in the brain, and disregulation of the dopamine neurocircuitry is associated with various neuropsychological disorders.