Generic placeholder image

Recent Patents on CNS Drug Discovery (Discontinued)

Editor-in-Chief

ISSN (Print): 1574-8898
ISSN (Online): 2212-3954

PTI-609: A Novel Analgesic that Binds Filamin A to Control Opioid Signaling

Author(s): Lindsay H. Burns and Hoau-Yan Wang

Volume 5, Issue 3, 2010

Page: [210 - 220] Pages: 11

DOI: 10.2174/157488910793362386

Price: $65

Abstract

Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors 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, dualfunction new chemical entity should not only be easier to develop but also more consistently efficacious than opioids combined with ultra-low-dose naltrexone. This new class of compounds, as well as the concept, screening assay and pharmacophore model, are covered in a family of recent patent applications.

Keywords: Analgesia, conditioned place preference, cytokine, filamin A, inflammation, signaling.


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy