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Pain Management 2016
October 03-04, 2016
Volume 5, Issue 5(Suppl) J Pain Relief
ISSN: 2167-0846 JPAR, an open access journal
conferenceseries .com
October 03-04, 2016 Vancouver, Canada
International Conference on
Pain Research & Management
Victor J Hruby, J Pain Relief 2016, 5:5(Suppl)
Design of novel multivalent ligands for the treatment of prolonged and neuropathic pain without
toxicities or development of tolerance or addiction
Victor J Hruby
University of Arizona, USA
Pain is the most ubiquitous disease in the world with over 1.5 billion people suffering from it every day. Though there are
treatments for acute pain, there are no good general treatments for prolonged and neuropathic pain. Current treatments for
prolonged pain eventually lead to tolerance and often addiction, and many other undesirable side effects. To overcome these
problems, we have taken a new approach in which we target multiple receptors in ascending and descending pain pathways in
the periphery and centrally. We have designed novel peptide and peptidomimetic ligands which have multiple pharmacophores
for receptors that are found in the disease state. For example, we have designed ligands that have potent agonist activities at mu
and delta opioid receptors, and potent antagonist activities like neurokinin 1 receptors, all in a single molecule. In addition to
extensive in vitro pharmacology on these ligands (9 or more different assays), we have done extensive in vivo studies in animal
models of prolonged and neuropathic pain. We have shown that properly designed ligands with novel bioactivity profiles are
potent analgesics which do not develop tolerance or addiction (as for example, morphine does), do not lead to inhibition of
transit through the gut, cross the blood brain barrier and do not create other toxicities of current drugs. The difficulties and
strategies for multivalent design in a single molecule will be discussed.
Biography
Victor J Hruby and his group have been developing a multidisciplinary approach to the study of peptide hormones and neurotransmitters and their receptors (mostly
GPCRs), which has as its major goal developing an understanding of the chemical/physical basis for their effects on human health and disease. This research has
involved close collaboration with biologists and medical doctors. They seek to develop peptide and peptidomimetic agonist, antagonist, and inverse agonist ligands
that are conformationally constrained and stable in biological environments, can cross (or not) membrane barriers including the blood brain barrier and have unique
biological profiles in vivo. They have been highly successful and developed state-of-the-art peptide and peptidomimetic synthesis; asymmetric synthesis of novel
chi constrained amino acids, β-turn mimetics, etc. and their chimeric derivatives; computational chemistry and molecular modeling including binding to GPCRs
of interest; development of state-of-the-art NMR methods to study peptide and peptidomimetic conformations in solution and in membrane environments, and
conformations when interacting (binding) to their receptors.