We have previously shown that Met5-enkephalin-Arg6-Phe7 (YGGFMRF) is metabolized by dipeptidyl carboxypeptidase and aminopeptidase. In this study we have searched for an effective enzyme inhibitor that is capable of crossing the blood brain barrier and blocking the inactivation of YGGFMRF by the dipeptidyl carboxypeptidase in CNS. HOE 498 was found to be a potent inhibitor of this enzyme. This compound was tested for its ability to cross the blood brain barrier. The presence of HOE 498 in rat cerebrospinal fluid (CSF) was demonstrated after I.V. or I.P. injection. The presence of HOE 498 in brain was also demonstrated by the increased recovery of YGGFMRF injected into the brain of rats pretreated I.P. with the inhibitor. Further-more, the recovery of YGGFMRF released from striatal tissue slices was increased in the presence of HOE 498. Whether this inhibitor can potentiate the analgesic effect of YGGFMRF still remains to be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH001555-05
Application #
4696404
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code