Our Approach

Medicinal Chemistry Group

Although the opioid system in animals consists of four distinct receptor systems, our studies focused on ligands for only the δ- and µ-opioid receptors due to their importance as antinociceptive drugs, their role in addiction, and multitude physiological mechanisms including psychological rewards.

While both receptor types provide analgesia, only the µ-opioid receptors lead to tolerance and dependency; the δ-opioid receptor-mediated bioactivity appears not to be involved in drug dependency, even through the receptors form complexes in the membrane that modulates their inherent activities. Thus, we embarked on the production of highly potent and selective µ- and δ-opioid agonists and antagonists, or classes of compounds referred to as having mixed properties (agonist/antagonist) or dual (agonism or antagonism) for these receptors. In order to pass through membrane barriers, the compounds needed to be stable, relatively low molecular weight and hydrophobic since the objectives are to relieve chronic or acute pain stemming from cancer, trauma or postoperative surgery, or to relieve addictive medical syndromes without the risks or tolerance, dependency and deleterious side-effects.

Considering that physical pain and that elicited by distress of social exclusion occur in the same region of the brain, the application of opioids in distress or anxiety management or other phenomena in different aspects of human health have yet to be fully explored. Furthermore, the use of judicious application of selective opioid antagonists as drugs co-administered with other chemical agonists might combat drug addiction, and ameliorate alcohol and excessive food intake to reduce the obesity epidemic in the US that also grows globally. Thus, we sought to develop dual bifunctional opioids containing antagonist/agonist bioactivities for different opioid receptor types that would enable simultaneous abatement and treatment of a specific opioid-dependent syndrome without detrimental side-effects.