Antidepressant effect of norepinephrine uptake 2 inhibitors and combined medications including them

US6403645B2 · kind B2 · utility

Assignee

• President and Fellows of Harvard College · US

Inventors

• Joseph Schildkraut · Sharon, US
• John J. Mooney · Wyckoff, US

Key dates

• Filing date: Mar 16, 2001
• Grant date: Jun 11, 2002
• Expiry date: Mar 16, 2021

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K45/06
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Norepinephrine uptake 2 inhibitors (or their precursors) are administered to enhance the effect of norepinephrine reuptake inhibitors and other antidepressants. The uptake 2 inhibitor may be combined in a single medication with a norepinephrine reuptake inhibitor, such as imipramine, desipramine, or reboxetine, in order to inhibit both uptake mechanisms. The norepinephrine uptake 2 inhibitors may also be combined with MAO inhibitors or with selective serotonin reuptake inhibitors. Alternatively, the norepinephrine uptake 2 inhibitors may be useful antidepressants in their own right, without the need for co-administration of other antidepressants. One class of norepinephrine uptake 2 inhibitors is normetanephrine (the O-methylated metabolite of norepinephrine) and normetanephrine precursors [such as 3(4-hydroxy-3-methoxyphenyl)-serine (4H-3MePS ), particularly L-threo-3-(4-H-3 MePS)] that are transported to the brain where they are converted into normetanephrine, thereby enhancing the effect of other antidepressants. For example, the invention enhances the antidepressant effect of norepinephrine reuptake inhibitors.