Author/Authors :
Bertrand Le Bourdonnec، نويسنده , , Christopher W. Ajello، نويسنده , , Pamela R. Seida، نويسنده , , Roberta G. Susnow، نويسنده , , Joel A. Cassel، نويسنده , , Serge Belanger، نويسنده , , Gabriel J. Stabley، نويسنده , , Robert N. DeHaven، نويسنده , , Diane L. DeHaven-Hudkins، نويسنده , , Roland E. Dolle، نويسنده ,
Abstract :
Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.
