154 results match your criteria: "Vanderbilt Center for Addiction Research[Affiliation]"
Pregnancy Intention and Maternal Alcohol Consumption.
Obstet Gynecol
April 2017
Department of Pediatrics, the Mildred Stahlman Division of Neonatology, the Vanderbilt Center for Health Services Research, the Department of Health Policy, the Vanderbilt Center for Addiction Research, the Institute for Medicine and Public Health, the Department of Biostatistics, and the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee.
Objective: To evaluate whether women planning a pregnancy are less likely to use alcohol in early pregnancy than those with unintended pregnancies.
Methods: Right From the Start (2000-2012) is a prospective, community-based pregnancy cohort. Maternal demographic, reproductive, and behavioral data were collected in telephone interviews at enrollment (mean±standard deviation 48±13 days of gestation) and later in the first trimester (mean±standard deviation 85±21 days of gestation).
Continued optimization of the M NAM ML375: Discovery of VU6008667, an M NAM with high CNS penetration and a desired short half-life in rat for addiction studies.
Bioorg Med Chem Lett
March 2017
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology and Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA. Electronic address:
Article Synopsis
- The letter discusses the optimization of a compound called M NAM ML375, which is useful for in vivo studies but has a problematic long elimination half-life in rats.
- The goal was to find a compound similar in potency to ML375 but with a much shorter half-life of less than 4 hours for better use in addiction research.
- The solution involved modifying the compound by adding a methyl group to create (S)-11 (VU6008667), which showed comparable potency, improved central nervous system penetration, and a significantly reduced half-life of 2.3 hours in rats.
Preclinical voluntary drinking models for alcohol abstinence-induced affective disturbances in mice.
Genes Brain Behav
January 2017
Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
Negative reinforcement is widely thought to play an important role in chronic alcohol-use disorders (AUDs), and high comorbidity between AUDs and affective disorders highlights the importance of investigating this relationship. Prominent models posit that repeated cycles of alcohol (ethanol, EtOH) exposure and withdrawal produce circuit adaptations in the central nervous system that drive a transition from positive- to negative reinforcement-based alcohol seeking. Evidence supporting this theory has accumulated in large part using forced EtOH administration models, such as chronic intragastric gavage and chronic vapor inhalation.
View Article and Find Full Text PDFLigand-based virtual screen for the discovery of novel M5 inhibitor chemotypes.
Bioorg Med Chem Lett
September 2016
Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address:
Article Synopsis
- The letter discusses a ligand-based virtual screening campaign targeting M5 NAMs, specifically ML375 and VU6000181, using SAR data.
- A library of 98,000 compounds was virtually screened using both QSAR and shape scores, but only a combined consensus score identified a promising new compound, VU0549108, which is a weak inhibitor of M5 mAChR.
- Binding studies indicate that VU0549108 interacts with the orthosteric site, though its effectiveness is limited and analogs show poor results, suggesting that further exploration for new chemotypes is needed.