Some piperdines have been shown to block
the DAT without being reinforcing, or addictive. The hypothesis
of Dr. Harp’s project is that piperdine derivatives of cocaine
analogs will be high potency inhibitors of the DAT and the serotonin
transporter (SERT), but will have very low abuse potential.
The long range goal of the project is to submit compounds that
have appropriate profiles and lack abuse potential to the
National Institute on Drug Abuse (NIDA) Division of
Treatment Research and Development for further testing
as potential therapeutic agents for cocaine addiction.
This plan is greatly facilitated by the presence of a very
successful drug abuse program at the Wake Forest School
of Medicine, including the NIDA- and National Institute on
Alcohol Abuse and Addiction (NIAAA)-funded centers
for alcoholism research.
Cocaine analogs, called tropanes, have high potency for
blocking the dopamine transporter (DAT) and have a long
duration of action, which is desirable for a therapeutic drug,
but some of them are also self-administered by animals,
and this makes them less desirable. Removal of the two-carbine bridge
of tropanes gives rise to piperdines.
Wake Forest University School of Medicine School Collaborator:
Sara Jones, Ph.D.
