Victor J Hruby
University of Arizona, USA
Title: Design of novel multivalent ligands for the treatment of prolonged and neuropathic pain without toxicities or development of tolerance or addiction
Biography
Biography: Victor J Hruby
Abstract
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.
