Kappa opioid antagonists have the potential to be developed as a pharmacotherapy for cocaine abuse. Antagonists of the kappa receptor system are needed to fully study the kappa opioid receptor system to develop a pharmacotherapy for cocaine abuse. Kappa opioid antagonists are both few in number and have associated problems with onset and a long duration of action. The goal of this research is to develop novel kappa opioid antagonists with excellent kappa opioid antagonist activity that also have a shortened duration of action. The approach to be used consists of developing kappa antagonists with metabolically labile groups which will produce the desired shortened duration of action. The current hypothesis is that the labile group attached to a kappa antagonist, once metabolized, will produce a compound which has no opioid activity. Thus, the parent compound will have kappa opioid antagonist activity and the metabolite will be devoid of kappa opioid activity. The duration of action will then depend strictly upon the rate metabolism leading to a shortened duration of action kappa antagonist.
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