An Open ‐Label Positron Emission Tomography (PET) Study to Evaluate Serotonin Transporter Occupancy Following Escalating Dosing Regimens of (R)‐(‐)‐O‐desmethylvenlafaxine and Racemic O‐Desmethylvenlafaxine

Conclusion: In vitro data suggests a ratio of 3.3:1 for binding at human SERT for SEP‐227162 relative to ODV. Our study suggests a ratio of 1.7:1, highlighting the value of in vivo imaging in the drug development process. This article is protected by copyright. All rights reserved. It has been shown that minimally effective doses of SSRIs (including paroxetine, sertraline, citalopram, fluoxetine, venlafaxine) responsible for antidepressant activity clinically correspond to steady‐state serotonin transporter (SERT) occupancies of ∼80%. This study examined the SERT occupancy of SEP‐227162, an enantiomer of desvenlafaxine (Pristiq™, Wyeth), as well as the racemic compound, desvenlafaxine. SEP‐227162 did achieve > 80% occupancy, but at doses which were ∼ 2x those of the racemic compound highlighting the value of in vivo imaging in the drug development process for initial dosing decisions.
Source: Synapse - Category: Neurology Authors: Tags: Research Article Source Type: research