The NIMH Toxicological Evaluation of Novel Ligands Program accelerates the discovery, development, and application of novel ligands for PET, SPECT, and MRI imaging in humans by providing toxicology and safety assessment of promising, target-selective compounds. The program also provides limited assessment 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 Investigational New Drug (IND) application to the Food and Drug Administration (FDA), or for Radioactive Drug Research Committee (RDRC) evaluation of a compound for human studies. The contract will evaluate toxicity and safety of compounds submitted for testing. This may include (but is not limited to) novel chemical entities, structural analogs of compounds with an IND, or analogs of FDA-approved drugs.
A broad range of tasks is available to assess the safety and/or pharmacokinetics of each ligand or drug. Capabilities available to investigators include:
- Validation of the analytical methods for quantitating drug concentrations in dosing solutions, biological fluids, and tissues, as required. Determination of plasma drug levels in animals administered the agent under study, and calculation of pharmacokinetic parameters derived from these data.
- Determination of bioavailability of the drug after different routes of administration, including oral, intravenous (IV), subcutaneous (SC), intramuscular (IM), or intraperitoneal (IP), as needed.
- Calculation of the pharmacokinetic parameters from the derived data.
- In vitro evaluation of hepatotoxicity in human and animal liver cells.
- Preclinical acute toxicity evaluations on lead compounds, evaluating clinical observations, body weights, clinical pathology, histopathology, and plasma drug levels in rodents and non-rodent species. Other toxicology endpoints may be selected if needed.
- Subacute and subchronic toxicity evaluations in rodents and large animal species, evaluating clinical observations, body weights, clinical pathology, and histopathology.
- Genotoxicity assessments using a battery of appropriate assays.
Since these preclinical studies are needed to demonstrate to the FDA that a candidate medication or imaging agent is understood well enough for designing appropriate clinical treatment regimens, most of the work to be conducted to achieve these objectives must be performed and the resulting data analyzed and reported in strict compliance with the FDA’s Good Laboratory Practice (GLP) regulations for nonclinical laboratory studies (21 CFR 58). These data must be obtained by carefully planned and skillfully executed methods that are specific, accurate, and precise. The applicable portions of the accumulated safety data will be included in documents submitted to the FDA in support of regulatory applications.
Hanna Ng, Ph.D.
Director of Preclinical Safety
333 Ravenswood Avenue
Menlo Park, CA, USA 94025
Phone: (650) 859-3676
NIMH Project Officer
National Institute of Mental Health
6001 Executive Boulevard
7N-7187, MSC 9641
Bethesda, MD 20857 USA
Phone: (301) 443-5288
Fax: (301) 402-4740