Medications Discovery Research Branch - The Intramural Research Program of the National Institute on Drug Abuse

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Molecular Targets and Medications Discovery BRANCH

Branch Overview

Branch Chief: Amy Hauck Newman, Ph.D. on-site page link

The Molecular Targets and Medications Discovery Branch investigates behavioral and pharmacological mechanisms underlying the effects of drugs, such as cocaine and methamphetamine that lead to their abuse and to drug dependence. Studies of the behavioral effects of drugs, including their reinforcing and subjective effects, are designed to provide new insights into the functioning of psychoactive agents in the central nervous system (CNS), and how those actions may lead to drug abuse. Novel, small molecules are designed and synthesized as pharmacological tools to study neurochemical targets in the brain, and actions at those targets are related to the behavioral effects of abused drugs. Current targets of interest are the dopamine and serotonin transporters, dopamine (D1, D2, D3), mGluR5, and sigma receptors. The analyses of in vitro and in vivo effects of target-selective compounds provides a relation between mechanism and behavior that has led to the discovery of compounds that may prove to be leads for the development of pharmacological treatments for drug dependence and other disorders of the CNS.

Medicinal Chemistry Section - click for larger version
Medicinal Chemistry Section - click for larger version

Lab Page

Medicinal Chemistry Section

Section Chief: Amy Hauck Newman, Ph.D. on-site page link

Design, synthesis and pharmacological evaluation of:

  • Atypical dopamine uptake inhibitors that bind with high affinity and selectivity to the dopamine transporter but are not cocaine-like in animal models of psychostimulant abuse
  • Dopamine D3 receptor antagonists and partial agonists as in vivo tools for the elucidation of the role these receptors play in addiction and impulsive behaviors
  • Allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5) as potential leads toward medications to treat drug addiction
  • Fluorescent ligands to study structure and function of the dopamine and serotonin transporters

Psychobiology Section

Section Chief: Jonathan L. Katz, Ph.D. on-site page link
  • Behavioral analysis of drug abuse using various procedures with animals, including intravenous drug self-administration, drug discrimination, and conditioned place preference.  These procedures are used to assess mechanisms involved in the abuse of drugs.
  • The relation between pharmacodynamic actions in the CNS, assessed using various techniques including in vivo microdialysis and in vivo binding and behavioral effects of abused drugs.
  • Quantitative radioligand binding and in vitro functional assays to assess target affinity and selectivity of compounds designed to elucidate mechanisms underlying the behavioral effects of abused drugs.
  • The application of these methods to provide new insights into the functioning of behaviorally active agents in the CNS and how these actions may lead to drug abuse, and how actions of novel compounds may be used to discover new treatments for drug dependence.

Integrative Neurobiology Section - Cick for largerIntegrative Neurobiology Section - Click for larger version

Integrative Neurobiology Section

Section Chief: Sergi Ferré, M.D., Ph.D. on-site page link

Projects include:

  • Functional and pharmacological significance of neurotransmitter receptor heteromers with in vivo approaches.
  • Molecular interactions involved in the quaternary structure and function of neurotransmitter receptor heteromers (cellular and molecular approaches).

Designer Drug Research UnitDesigner Drug Research Unit - Click for larger version

Designer Drug Research Unit

Chief: Michael H. Baumann, Ph.D.

Topics of investigation include:

  • Pharmacology of newly-emerging designer drugs of abuse, such as “bath salts” stimulants and “K2/Spice” cannabinoids
  • Structure-activity relationships for ligands interacting at monoamine transporter proteins
  • Mechanisms underlying neurotoxic effects of stimulant drugs of abuse

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The National Institute on Drug Abuse (NIDA), is part of the National Institutes of Health (NIH), the principal biomedical and behavioral research agency of the United States Government. NIH is a component of the U.S. Department of Health and Human Services.

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