Bupropion is a safe and generally well-tolerated treatment for depression and nicotine dependence when used in doses <400mg/day. However, at higher doses, bupropion has an increased risk of seizure that may limit the ability of the drug to realize its maximum potential. Bupropion is extensively metabolized in man and in animals. The resulting hydroxybupropion (OHB) differs among man, rat and mouse. The metabolism is extensive with circulating OHB at 15-20 fold higher levels than parent bupropion. Application of chiral chromatography has determined that >95 percent of circulation OHB is the levorotatory enantiomer (-OHB). Studies, in-house, have demonstrated that -OHB is devoid of therapeutic activity but is 3-fold more toxic than +OHB. The present proposal is predicated on the hypothesis that formation of -OHB is enantioselective from (S)-bupropion and that the metabolism of (R)-bupropion, while much less acile, primarily results in +OHB. Studies, with human microsomes, are proposed to test this hypothesis. If successful, a Phase II submission will request support to conduct a proof-of-concept study in humans.

Proposed Commercial Applications

NOT AVAILABLE

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43MH065763-01
Application #
6486394
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (10))
Program Officer
Grabb, Margaret C
Project Start
2002-04-10
Project End
2002-10-31
Budget Start
2002-04-10
Budget End
2002-10-31
Support Year
1
Fiscal Year
2002
Total Cost
$134,150
Indirect Cost
Name
Trelion Pharmaceuticals, Inc.
Department
Type
DUNS #
City
Research Triangle Park
State
NC
Country
United States
Zip Code
27709