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There are currently no registered drugs that slow the progression of neurodegenerative diseases, in part because translation from animal models to the clinic has been hampered by poor distribution to the brain. The present studies examined a selected series of para-phenyl–substituted diindolylmethane (C-DIM) compounds that display anti-inflammatory and neuroprotective efficacy in vitro. We postulated that the pharmacokinetic behavior of C-DIM compounds after oral administration would correlate with neuroprotective efficacy in vivo in a mouse model of Parkinson’s disease. Pharmacokinetics and metabolism of 1,1-bis(3′-indolyl)-1-(p-methoxyphenyl)methane (C-DIM5), 1,1-bis(3′-indolyl)-1-(phenyl)methane, 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (C-DIM8), and 1,1-bis(3′-indolyl)-1-(p-chlorophenyl)methane (C-DIM12) were determined in plasma and brain of C57Bl/6 mice after oral and …