Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2003-09-10
2004-10-05
Powers, Fiona T. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S375000, C546S090000, C548S218000
Reexamination Certificate
active
06800637
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to antidepressant indolealkyl derivatives of heterocycle-fused benzodioxan methylamines, to processes for preparing them, methods of using them and to pharmaceutical compositions containing them.
BACKGROUND OF THE INVENTION
Major depression is a serious health problem affecting more than 5% of the population, with a lifetime prevalence of 15-20%.
Selective serotonin reuptake inhibitors have produced success in treating depression and related illnesses and have become among the most prescribed drugs. They nonetheless have a slow onset of action, often taking several weeks to produce their full therapeutic effect. Furthermore, they are effective in less than two-thirds of patients.
Serotonin selective reuptake inhibitors (SSRIs) are well known for the treatment of depression and other conditions. SSRIs work by blocking the neuronal reuptake of serotonin, thereby increasing the concentration of serotonin in the synaptic space, and thus increasing the activation of postsynaptic serotonin receptors.
However, although a single dose of an SSRI can inhibit the neuronal serotonin transporter which would be expected to increase synaptic serotonin, long-term treatment is required before clinical improvement is achieved.
It has been suggested that the SSRIs increase the serotonin levels in the vicinity of the serotonergic cell bodies and that the excess serotonin activates somatodendritic autoreceptors, 5HT
1A
receptors, causing a decrease in serotonin release in major forebrain areas. This negative feedback limits the increment of synaptic serotonin that can be induced by antidepressants.
A 5HT
1A
antagonist would limit the negative feedback and should improve the efficacy of the serotonin reuptake mechanism (Perez, V., et al.,
The Lancet,
349:1594-1597 (1997)). Such a combination therapy would be expected to speed up the effect of the serotonin reuptake inhibitor.
Thus, it is highly desirable to provide improved compounds which both inhibit serotonin reuptake and which are antagonists of the 5HT
1A
receptor.
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Evrard Deborah Ann
Stack Gary Paul
Webb Michael Byron
Zhou Dahul
Powers Fiona T.
Woodcock & Washburn LLP
Wyeth
LandOfFree
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