Intern
    Prof. Dr. Reinhold Tacke

    Sila-venlafaxine

      

    Sila-venlafaxine: A Silicon Analogue of the Serotonin/Noradrenaline Reuptake Inhibitor Venlafaxine

    Synthesis of Sila-venlafaxine

    Serotonin, Noradrenaline, and Dopamine Reuptake Inhibition (Enantiomers of Venlafaxine and Sila-venlafaxine)

    In vitro Efficacy as Determined by Radioligand Transporter Assays Using Recombinant Human Monoamine Transporter Proteins. pIC50 Denotes the Negative Decadic Logarithm of the Half-Maximum Effect Concentration [M].

    In vitro Pharmacological Profile of (R)-Sila-venlafaxine

     

    (R)-Sila-venlafaxine is a selective noradrenaline reuptake inhibitor.

    In vitro tests across a panel of 68 common receptors/channels and 16 enzymes:
    (R)-Sila-venlafaxine is inactive in all assays (< 50% inhibition at 10 µM) except for weak affinity at Ca2+ and Na+ channels.

     

    Evaluation of (R)-Sila-venlafaxine in a Ferret Model of Morphine-Induced Emesis

    (R)-Sila-venlafaxine was dosed orally in ferrets 2 h prior to the emetogen (morphine, 0.125 mg/kg, s.c.; group size, n = 4). The ferrets were monitored for emetic episodes (retching and vomiting events) for 2 h following the administration of morphine.


    At 50 mg/kg (R)-sila-venlafaxine completely abolishes emetic episodes, and almost complete inhibition (93%) is achieved at 5 mg/kg.

    Patent:

    G. A. Showell, D. Miller, A. K. Mandal, R. Tacke, J. O. Daiss (Inventors), Amedis Pharmaceuticals Ltd., Cambridge, U.K., PCT Int. Pat. Appl. WO 2004/094436 A1 (04.11.2004). more ...

    Publications:

    J. O. Daiss, C. Burschka, J. S. Mills, J. G. Montana, G. A. Showell, J. B. H. Warneck, R. Tacke, Organometallics 2006, 25, 1188–1198. more ...
    J. O. Daiss, M. Penka, C. Burschka, R. Tacke, Organometallics 2004, 23, 4987–4994. more ...
    G. A. Showell, M. J. Barnes, J. O. Daiss, J. S. Mills, J. G. Montana, R. Tacke, J. B. H. Warneck, Bioorg. Med. Chem. Lett. 2006, 16, 2555–2558. more ...

    J. B. Warneck, F. H. M. Cheng, M. J. Barnes, J. S. Mills, J. G. Montana, R. J. Naylor, M.-P. Ngan, M.-K. Wai, J. O. Daiss, R. Tacke, J. A. Rudd, Toxicology and Applied Pharmacology, 2008, in press.