MEDI 42 |
| The 5HT6 receptor is the latest serotonin receptor identified by molecular cloning. Its mRNA appears to be distributed in the brain, making it an attractive CNS therapeutic target. SUVN-504 is a highly selective 5-HT6 receptor antagonist with high affinity for the human receptor (pKi 3.15 nM) and is orally bioavailable in rats. Effective lead-optimization of critical physico-chemical properties has led to the high brain penetration index. The present study describes the in vivo brain penetration of the SUVN-504 in the male wistar rats. SUVN-504 was administered through femoral vein at a constant infusion rate over 12 hr at target dose rate of 1 mg/kg/hr. Blood samples were collected to confirm steady-state blood concentrations. Blood and brain samples were analyzed by LC-MS/MS. SUVN-504 produced with a brain-blood ratio of 13:1 in rats with high oral bioavailability. Therefore, SUVN-504 is selected for further development. |
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |