PTI-609: a novel analgesic that binds filamin A to control opioid signaling.

PTI-609: a novel analgesic that binds filamin A to control opioid signaling. Recent Pat CNS Drug Discov. 2010 Nov;5(3):210-20 Authors: Burns LH, Wang HY Abstract Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors (MORs) so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemical entity that binds filamin A with picomolar affinity and also activates opioid receptors via a novel binding domain. PTI-609 and analogs have similar analgesic efficacy to morphine by oral administration in mice, provide some anti-inflammatory activity in the rat collagen-induced arthritis model, and show no conditioned place preference at analgesic doses, suggesting no potential for abuse and addiction. PTI-609 was designed after discovering filamin A as the high-affinity target of naltrexone or naloxone. Combined with opiates, ultra-low-dose naloxone or naltrexone can enhance and prolong the analgesia of the opiate alone and prevent or attenuate opioid tolerance, dependence and addictive properties. We will review here the mechanism of action of ultra-low-dose naltrexone and naloxone, the discovery of filamin A as their high-affinity target, and the rationale as to why the current...
Source: Recent Patents on CNS Drug Discovery - Category: Drugs & Pharmacology Tags: Recent Pat CNS Drug Discov Source Type: research