Carolyn Fairbanks, Ph.D., of University of Minnesota will present a lecture entitled: Impact of Agmatine-Based Therapeutics on Opioid Pharmacology and Chronic Pain.
Abstract: NMDAR antagonism inhibits and reverses the neuroplasticity associated with chronic pain, but such reversal is often transient and is frequently accompanied by motor side effects. The decarboxylated form of L-arginine, agmatine, antagonizes NMDA receptors, inhibits nitric oxide synthase, and reverses behavioral manifestations of neuroplasticity. We have pursued two strategies to develop agmatine-based therapeutics. Through our first approach we expressed the proposed synthetic enzyme for agmatine in regions relevant to the sensory pathway in order to provide ultra-local control of neuroplasticity associated with chronic pain. In our second approach we developed new strategically substituted agmatines for improved biopharmaceutical features relative to the parent compound. The presentation will feature pharmacological data from both approaches that demonstrate alleviation of neuropathic pain, reduction of opioid tolerance and self-administration and lack of motor side effects. Additionally, our data suggest the effects to be dependent on the NR2B receptor subunit of the NMDA receptor. Development of these therapeutic approaches that exert inhibitory control of the neuroplasticity associated with chronic pain and opioid tolerance may yield important novel non-opioid pain relieving options.