Paraxanthine,caffeine的代谢物,可通过刺激Ryanodine受体通道来抑制多巴胺能细胞的死亡。WhenParaxanthine(PX)isappliedtotheculturesforaprolongedperiod,thenumberofTH+neuronsisaugmentedinadose-dependentmanner.TheeffectofParaxanthine,alreadysignificantat100μM,increasesgraduallyandremainsoptimalbetween800and1000μM,at10DIV.CountsofTH+neuronsperformsatdifferentstagesofmaturationoftheculturesindicatethatParaxanthinemostlikelypreventsDAcellloss.GDNF,aprototypicaltrophicfactorforDAneurons,isonlyslightlymoreeffectivethan800μMParaxanthineinrescuingDAneuronsafter10and16DIVwhenusedatanoptimalconcentrationof20ng/mL.About80%ofcaffeineisN3-demethylatedtoformParaxanthine,UnlikeParaxanthine,caffeineispoorlyeffectiveinprotectingDAneuronsfromdeathForexample,ataconcentrationof800μM,caffeineproducesonlyamodest40%increaseinthenumberofTH+cellsat10DIV,whereasthesameconcentrationofParaxanthineoptimallypromotesDAcellsurvival(169%increase).
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