Drugs targeting ion channels already generate over 6 billion dollars in sales per annum. According to the FDA, the number of new approved drugs targeting ion channels is equal to or even higher than that for drugs targeting proteases, polymerases and reverse transcriptases. But, despite their remarkable physiological value, ion channels have remained a relatively unexploited therapeutic target class, especially in comparison to target areas such as G-protein coupled receptors or kinases (for a full analysis of opportunities surrounding ion channel therapeutics click here). One area that is responsible for the growth in research surrounding ion channels is chronic pain.

Approximately 9% of the US population suffer from moderate to severe non-cancer-related pain, a figure that includes 40-70 million individuals with chronic pain. This condition precipitates other serious pathologies such as depression and is associated with an estimated pharmaceuticals market of US$18.7 billion worldwide. Since chronic pain is notoriously difficult to treat using currently available therapeutics, the development of analgesics has represented a major pharmaceutical objective. (click here for "Pain 2002" an analysis of future directions in analgesic therapeutics). The origins of pain range from nociceptive (caused by tissue injury or inflammation) to neuropathic, a condition that can have many underlying causes. Approximately 26 million patients worldwide (10 million in the US) suffer from some form of neuropathic pain, spending an estimated $2-3 billion annually on treatments.

One ion channel modulator that has recently entered phase I evaluation for the treatment of pain is Newron’s NW-1029, a benzylamino propanamide derivative, that was selected among several molecules of this chemical class on the basis of its affinity for the [(3)H]batracotoxin ligand displacement of the Na(+) channel complex and also on the basis of its voltage and use-dependent inhibitory action on the Na(+) currents of the rat DRG sensory neuron. Most recently Newron scientists have evaluated the analgesic activity of NW-1029 in animal models of inflammatory and neuropathic pain as well as in acute pain tests. Orally administered NW-1029 dose-dependently reduced indices of hyperalgesia in both the inflammatory and the neuropathic pain models at doses below 1mg/kg (po). No effects were observed in the hot-plate and tail-flick tests of acute pain up to 30 mg/kg p.o. The compound orally administered was well tolerated, without signs of neurological impairment up to high doses. These results indicate that NW-1029 has anti-nociceptive properties in models of inflammatory and neuropathic pain supporting its entry into phase I evaluation.

Entry date Tuesday, April 08, 2003

Adapted from Veneroni et al, Pain 2003 Mar;102(1-2):17-25 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk