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Molecular Pharmacology Research Program

This program supports research aimed at the discovery, design, development, and testing of novel compounds for use as pharmacological research tools or candidate therapeutics for mental illnesses. Areas of interest include:

  • Studies on the design, synthesis, and characterization of ligands for novel and emerging targets relevant to mental illnesses.
  • Isolation, identification, and characterization of compounds derived from natural products.
  • Molecular modeling and computational chemistry.
  • Isolation and characterization of endogenous ligands.
  • Preliminary evaluation of candidate compounds using screening assays (e.g., biochemical and cellular assays, modified model organisms, and electrophysiological or behavioral systems).
  • Development and evaluation of novel chemical delivery systems.

High-priority areas include the development of probes and/or early drug leads for novel molecular or circuit-based targets relevant to mental illnesses, including targets identified through human genetic studies. Studies incorporating the use of novel assays to assess activity of ligands in relevant circuits, systems, and/or domains of function are encouraged. Incorporation of concurrent biomarker development is encouraged, when feasible, for early-stage drug discovery efforts.

Studies aimed at the development of new ligands for targets where a high-quality probe or therapeutic already exists are generally of lower priority.

This program also provides a range of research resources, including the screening of novel psychoactive compounds at CNS receptors, channels, and transporters; the synthesis and distribution of psychoactive compounds to support basic and clinical research; and the assessment of promising compounds for toxicity and safety for use in human studies. Research resources supported by the program include:

  • NIMH Psychoactive Drug Screening Program  —provides screening of novel psychoactive compounds for pharmacological and functional activity at cloned human or rodent CNS receptors, channels, and transporters. Assays are also available for bioavailability predictions (CaCo2, MDR-1) and cardiovascular toxicity predictions (HERG, 5-HT2B). The program also supports a database of affinity constants for ligand binding.
  • NIMH Chemical Synthesis and Drug Supply Program  —synthesizes and distributes novel research chemicals, psychoactive drugs, and compounds unavailable to the scientific community from commercial sources. The program also supports radiosynthesis, medicinal chemistry, and Good Manufacturing Practice synthesis of promising candidate compounds for use in clinical studies.
  • NIMH Toxicological Evaluation of Novel Ligands Program  —provides toxicology and safety assessment of promising, target-selective compounds for use as imaging ligands in human studies. The program also provides support for early drug and ligand discovery, including in vitro ADME and toxicology assays, pharmacokinetic assessment, and initial toxicity evaluation and limited Investigational New Drug (IND)-directed evaluation of novel psychoactive agents for clinical research and as potential therapeutics. Toxicology and safety data generated by the program will be used to support an IND application to the Food and Drug Administration (FDA), and for Radioactive Drug Research Committee (RDRC) evaluation of a compound for human studies.

It is recommended that applicants review the NIH/NIMH Therapeutics Discovery Research webpage for relevant announcements and guidance.

Applications should adhere to recently published recommendations detailed in a notice in the NIH Guide (NOT-14-004  ) and summarized in Enhancing the Reliability of NIMH-Supported Research through Rigorous Study Design and Reporting on the NIMH website.

Applicants are strongly encouraged to discuss their proposals with the Institute contact listed below prior to the submission of their application to ascertain that their proposed work is aligned with NIMH funding priorities.

Contact

Jamie Driscoll, B.A.
6001 Executive Boulevard, Room 7189, MSC 9641
301-443-5288, jdrisco1@mail.nih.gov