Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies

@article{Ratti2013FullCN,
  title={Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies},
  author={Emiliangelo Ratti and Paolo Bettica and Robert Alexander and Graeme Archer and David J. Carpenter and G. E. Evoniuk and Roberto Gomeni and Erica J. Lawson and Monica C. Lopez and Helen Millns and Eugenii A. Rabiner and David G. Trist and Mike Trower and Stefano Zamuner and R. Gokula Krishnan and Maurizio Fava},
  journal={Journal of Psychopharmacology},
  year={2013},
  volume={27},
  pages={424 - 434}
}
Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [11C]GR205171 binding indicated that oral orvepitant doses of 30–60 mg/day provided >99% receptor… 

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