TY - JOUR
T1 - Antidepressant-like actions of DOV 21,947
T2 - A "triple" reuptake inhibitor
AU - Skolnick, Phil
AU - Popik, Piotr
AU - Janowsky, Aaron
AU - Beer, Bernard
AU - Lippa, Arnold S.
N1 - Funding Information:
This work was supported in part by VA and NIH grants and interagency agreements to AJ.
PY - 2003/2/14
Y1 - 2003/2/14
N2 - DOV 21,947 [(+)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochloride] inhibits the reuptake of [3H]serotonin, [3H]norepinephrine, and [3H]dopamine in human embryonic kidney (HEK) 293 cells expressing the corresponding human recombinant transporters (IC50 values of 12, 23, and 96 nM, respectively). This compound also inhibits [125I]RTI 55 (3β-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester) binding to the corresponding transporter proteins in membranes prepared from these cells (Ki values of 99, 262, and 213 nM, respectively). DOV 21,947 reduces the duration of immobility in the forced swim test (using rats) with an oral minimum effective dose of 5 mg/kg. This antidepressant-like effect manifests in the absence of significant increases in motor activity at doses of up to 20 mg/kg. DOV 21,947 also produces a dose-dependent reduction in immobility in the tail suspension test, with a minimum effective oral dose of 5 mg/kg. The ability of DOV 21,947 to inhibit the reuptake of three biogenic amines closely linked to the etiology of depression may result in a therapeutic profile different from antidepressants that inhibit the reuptake of serotonin and/or norepinephrine.
AB - DOV 21,947 [(+)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochloride] inhibits the reuptake of [3H]serotonin, [3H]norepinephrine, and [3H]dopamine in human embryonic kidney (HEK) 293 cells expressing the corresponding human recombinant transporters (IC50 values of 12, 23, and 96 nM, respectively). This compound also inhibits [125I]RTI 55 (3β-(4-iodophenyl)tropane-2β-carboxylic acid methyl ester) binding to the corresponding transporter proteins in membranes prepared from these cells (Ki values of 99, 262, and 213 nM, respectively). DOV 21,947 reduces the duration of immobility in the forced swim test (using rats) with an oral minimum effective dose of 5 mg/kg. This antidepressant-like effect manifests in the absence of significant increases in motor activity at doses of up to 20 mg/kg. DOV 21,947 also produces a dose-dependent reduction in immobility in the tail suspension test, with a minimum effective oral dose of 5 mg/kg. The ability of DOV 21,947 to inhibit the reuptake of three biogenic amines closely linked to the etiology of depression may result in a therapeutic profile different from antidepressants that inhibit the reuptake of serotonin and/or norepinephrine.
KW - "Broad-spectrum" antidepressant
KW - 5-HT (5-hydroxytryptamine, serotinin)
KW - DOV 21,947
KW - Dopamine
KW - Norepinephrine
KW - Reuptake inhibitor
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U2 - 10.1016/S0014-2999(03)01310-4
DO - 10.1016/S0014-2999(03)01310-4
M3 - Article
C2 - 12586204
AN - SCOPUS:12244291291
SN - 0014-2999
VL - 461
SP - 99
EP - 104
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -