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.
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.
The National Institute on Drug Abuse's Medications Discovery Research Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize 4-phenylpiperazine derivatives as dopamine D3 selective ligands.
Modafinil has attracted attention for the treatment of cognitive dysfunction in disorders such as attention-deficit/hyperactivity disorder (ADHD) as well as cocaine and methamphetamine dependence. However, modafinil has relatively low affinity for binding to the dopamine transporter (DAT) to block dopamine reuptake, and is water-insoluble, thus requiring large doses to achieve pharmacological effects.
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 National Institute on Drug Abuse (NIDA) is seeking interested parties to license or co-develop GDNFOS peptides and non-coding RNAs as therapeutic agents for neurodegenerative diseases.
Typical MRI imaging sessions can last over 45 minutes and depend on the subject remaining still during the procedure for accurate imaging. In particular, animals being imaged, such as rodents (rats) in an awakened state, are not readily compliant with the restricted movement required when being imaged. Current techniques for imaging awake animals focus on training them with full body restraints and head fixation using a bite bar and/or ear bars.
Substance use disorder is a chronic medical condition, taking its toll on our public health care and judicial systems in an economically unsustainable way. More than 20 million Americans suffer from substance use disorders.
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).