AI Article Synopsis
- 6-Bromo-7-[(11)C]methylpurine interacts with glutathione in the brain, becoming a substrate for the efflux pump MRP1, which is important for studying drug resistance.
- The compound's conversion rate varies by species, indicating the need to modify its structure for accurate application in humans and other animals.
- Testing different halogenated and methyl-substituted derivatives showed significant differences in reactivity across mouse, rat, and monkey brains, enhancing potential for assessing MRP1 function in various species.
Article Abstract
6-Bromo-7-[(11)C]methylpurine is reported to react with glutathione via glutathione S-transferases in the brain and to be converted into a substrate for multidrug resistance-associated protein 1 (MRP1), an efflux pump. The compound with a rapid conversion rate allows quantitative assessment of MRP1 function, but this rate is probably susceptible to interspecies differences. Hence, for application to different species, including humans, it is necessary to adjust the conversion rate by modifying the chemical structure. We therefore designed 6-halo-9-(or 7)-[(14)C]methylpurine (halogen: F, Cl, Br, or I), and evaluated them in vitro with respect to enzymatic reactivity with glutathione using brain homogenates from the mouse, rat, or monkey. There was a marked difference in reactivity between these species. Changes in the position of the methyl group and halogen on N-methyl-6-halopurine provided various compounds possessing wide-ranging reactivity with glutathione. In conclusion, the adjustment of reactivity of 6-bromo-7-[(11)C]methylpurine may allow assessment of MRP1 function in the brain in various species.
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| http://dx.doi.org/10.1021/jm901332c | DOI Listing |
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