The treatment for the pain associated with terminal cancer remains poorly treated. Although opioids, such as morphine,, can trat the pain, chronic treatment with morphine leads to severe constipation. The goal of this research is to develop novel opioids which will treat severe pain, without leading to constipation. The approach to be used consists of developing opioids with a profile of mu agonism and delta antagonism, a profile shown to reduce the development of tolerance to the antinociceptiv4 effects of mu agonists. Thus the ever increasing dose of opioid will not b required, leading to lower levels of constipation. The current hypotheses is that the aromatic ring of the indolomorphinans and benzylidene-type delta selective opioids leads to a profile of low delta efficience. Thus, if a suitably placed aromatic ring is introduced into the structure of the orvinols (a class of opioids known to bind with high affinity to both mu and delta receptors), a profile of potent mu agonism and delta antagonism will result.
