Next Generation Quinoline Methanols and Mefloquine in Mice
Author Information
Author(s): Dow Geoffrey S, Milner Erin, Bathurst Ian, Bhonsle Jayendra, Caridha Diana, Gardner Sean, Gerena Lucia, Kozar Michael, Lanteri Charlotte, Mannila Anne, McCalmont William, Moon Jay, Read Kevin D, Norval Suzanne, Roncal Norma, Shackleford David M, Sousa Jason, Steuten Jessica, White Karen L, Zeng Qiang, Charman Susan A
Primary Institution: Walter Reed Army Institute of Research
Hypothesis
Can next generation quinoline methanols (NGQMs) be developed to have reduced central nervous system (CNS) exposure compared to mefloquine?
Conclusion
Reduction of CNS levels of NGQMs relative to mefloquine may be feasible.
Supporting Evidence
- Seven (28%) compounds exhibited acceptable whole brain concentrations.
- Two (8%) compounds exhibited acceptable free brain concentrations.
- Diamine quinoline methanols were identified as the most promising lead compounds.
Takeaway
Scientists are trying to create new malaria drugs that don't affect the brain as much as an old drug called mefloquine.
Methodology
The study measured plasma and brain levels of mefloquine and 25 modified NGQMs in male FVB mice after intravenous dosing.
Limitations
The study was conducted in mice, and results may not directly translate to humans.
Participant Demographics
Male FVB mice, six weeks old.
Statistical Information
P-Value
p<0.0001
Confidence Interval
0-21%
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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