"Broad spectrum" antidepressants: Is more better
for the treatment of depression?

by
Skolnick P, Popik P, Janowsky A, Beer B, Lippa AS.
DOV Pharmaceutical, Inc.,
433 Hackensack Avenue,
07601, Hackensack, NJ, USA
Life Sci. 2003 Nov 7;73(25):3175-9


ABSTRACT

The majority of antidepressants in current use selectively inhibit the reuptake of serotonin and/or norepinephrine. "Broad spectrum" antidepressants are compounds that inhibit the reuptake of norepinephrine, serotonin and dopamine, the three biogenic amines most closely linked to depression. The pharmacological profile of one such compound has recently been described (European Journal of Pharmacology, 461 (2003) 99). DOV 21,947, an azabicyclo[3.1.0]hexane, potently inhibits norepinephrine, serotonin and dopamine reuptake by the corresponding human transporter proteins. DOV 21,947 is orally active in the forced swim and tail suspension tests, preclinical procedures that are highly predictive of antidepressant action in patients. A closely related compound, DOV 216,303 is safe and well-tolerated in Phase I studies. The plasma concentrations of DOV 216,303 following both single and multiple doses appear sufficient to inhibit norepinephrine, serotonin, and dopamine reuptake. Based on the pivotal role proposed for dopamine in depression, it has been hypothesized that a broad spectrum antidepressant will produce a more rapid onset and/or higher efficacy than agents inhibiting the reuptake of serotonin and/or norepinephrine.
DOV 21,947
DOV 216,303
21st Century
Antidepressants
Mixed depression
Atypical depression
Retarded depression
New antidepressants
An individualised approach
Antidepressants: how fast?
Neurotransmitter transporters
Mood-brighteners and antidepressants
Long-term side effects of antidepressants
Pharmacogenomics and new antidepressants
Mood enhancement via stem cell therapy
Selective publication of clinical trials leads to unrealistic estimates of antidepressant efficacy


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