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                            Funding & Awards
 The Effects of Synthetic Cathinone Chirality on Pharmacodynamics and Pharmacokinetics and Its Implications for Forensic Toxicology
Award Information
Awardee
              VIRGINIA COMMONWEALTH UNIVERSITY
Award #
              2019-R2-CX-0046
Funding Category
              Competitive Discretionary
Location
                    RICHMOND, VA
Congressional District
              4
Status
              Closed
Funding First Awarded
              2019
Total funding (to date)
              $149,960
Original Solicitation
              Graduate Research Fellowship in Science, Technology, Engineering, and Mathematics, FY 2019
Description of original award (Fiscal Year 2019, $149,960)
As the attention in the United States is focused on the "opioid epidemic," the rise in the use and number of overdose deaths associated with stimulant drugs risks being overshadowed. The novel psychoactive substances being abused includes the beta-keto analogs of the amphetamine-type stimulants known as synthetic cathinones. Many synthetic cathinones, including methcathinone, contain a stereocenter at the alpha carbon. This introduces chirality to the molecule such that two spatial orientations of the molecule exist, and this has the potential for significant impacts to the interpretation of analytical data by the forensic toxicologist due to pharmacokinetic and pharmacodynamic differences between enantiomeric forms. The current research on synthetic cathinones largely focuses on racemic mixtures and typically does not distinguish between enantiomeric forms. This research will examine racemic methcathinone and its two enantiomers individually, as well as two novel compounds where chirality is removed by making substitutions upon the alpha carbon of the molecule. The researcher will accomplish three main objectives: (1) abuse liability will be assessed using intracranial self-stimulation in a rat model for each compound (2) analytical methodology will be developed and validated according to the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines for the stereospecific identification of these synthetic cathinones and their potential biomarkers in biological matrices and (3) the pharmacokinetics of these cathinonest specifically the metabolism, tissue distribution, and elimination, will be examined with respect to the stereochemistry of the molecules. These three research aims will provide the scientific and forensic communities with a greater understanding of synthetic cathinones and their stereochemistry to be used in forensic toxicological analysis, including providing both practical methods for analysis as well as pharmacological relationships to be used in the interpretation of toxicological findings in the context of legal investigations. This interdisciplinary project involves the collaboration of the Virginia Commonwealth University Departments of Forensic Science and Pharmacology and Toxicology to generate a robust set of data involving analytical chemistry and behavioral pharmacology. This research is anticipated to result in multiple publications in peer-reviewed journals and presentations at scientific conferences, as well as a doctoral dissertation.
Note: This project contains a research and/or development component, as defined in applicable law," and complies with Part 200 Uniform Requirements - 2 CFR  200.210(a)(14). ca/ncf



  
Grant-Funded Publications
        
                      Rate of onset of dopamine transporter inhibitors assessed with intracranial self-stimulation and in vivo dopamine photometry in rats
                  Opioid-like adverse effects of tianeptine in male rats and mice
                  Behavioral Screening and Chiral Bioanalysis of Emerging Stimulant-Type Drugs in Rats
                  Opioid-like adverse effects of tianeptine in male rats and mice
                  A strategy to prioritize emerging drugs of abuse for analysis: Abuse liability testing using intracranial self-stimulation (ICSS) in rats and validation with α-pyrrolidinohexanophenone (α-PHP)
                  A strategy to prioritize emerging drugs of abuse for analysis: Abuse liability testing using intracranial self-stimulation (ICSS) in rats and validation with α-pyrrolidinohexanophenone (α-PHP)

  
Date Created: September 16, 2019
    
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