title: Azepines and piperidines with dual norepinephrine dopamine uptake inhibition and antidepressant activity.
abstract: Herein, we describe the discovery of inhibitors of norepinephrine (NET) and dopamine (DAT) transporters with reduced activity relative to serotonin transporters (SERT). Two compounds, 8b and 21a, along with nomifensine were tested in a rodent receptor occupancy study and demonstrated dose-dependent displacement of radiolabeled NET and DAT ligands. These compounds were efficacious in a rat forced swim assay (model of depression) and also had activity in rat spontaneous locomotion assay.
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Dean G
authors.initials: DG
authors.lastname: Brown
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Bernstein
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Urbanek
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Becker
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Throner
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Dembofsky
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Steelman
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Lois A
authors.initials: LA
authors.lastname: Lazor
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Clay W
authors.initials: CW
authors.lastname: Scott
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Wood
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wesolowski
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Nugiel
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Koch
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Pivonka
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Carol
authors.initials: C
authors.lastname: Thompson
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Zacco
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Elmore
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Patricia
authors.initials: P
authors.lastname: Schroeder
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: JianWei
authors.initials: J
authors.lastname: Liu
authors.affiliation: Argenta , 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, CM19 5TR, United Kingdom.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hurley
authors.affiliation: Argenta , 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, CM19 5TR, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Ward
authors.affiliation: Argenta , 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, CM19 5TR, United Kingdom.
authors.forename: Hazel J
authors.initials: HJ
authors.lastname: Hunt
authors.affiliation: Argenta , 8/9 Spire Green Centre, Flex Meadow, Harlow, Essex, CM19 5TR, United Kingdom.
authors.forename: Karen
authors.initials: K
authors.lastname: Williams
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: McLaughlin
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Valerie
authors.initials: V
authors.lastname: Hoesch
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Simon
authors.initials: S
authors.lastname: Sydserff
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: Donna
authors.initials: D
authors.lastname: Maier
authors.affiliation: CNS Discovery Research, AstraZeneca Pharmaceuticals , 1800 Concord Pike, Wilmington, Delaware 19850-5437, United States.
authors.forename: David
authors.initials: D
authors.lastname: Aharony
keywords: antidepressant; dopamine; norepinephrine; uptake inhibitors