ADL5859 HCl

ADL5859 HCl is an δ-opioid receptor agonist (Ki=0.84 nM, EC50=20 nM). There are three known opioid receptors-µ, κ, and δ. All current opioid analgesics exert their effect mainly on the µ variant, with no presently-approved compounds targeted specifically at the κ, and δ types. Preclinical work suggests that δ-specific agonists may exhibit superior analgesic properties to µ agonists whilst avoiding some of their common and undesirable side-effects. ^[1]
ADL5859 HCl is an agonist agent that selectively stimulates the δ-opioid receptor with potential application in a wide range of inflammatory, neuropathic and acute pain conditions. In addition, Delta agonists are thought to modulate other biological processes that may manifest themselves in disease states or conditions such as overactive bladder and depression. ^[1]
ADL5859 HCl displayed subnanomolar binding affinity at the δ opioid receptor (Ki=0.84 nM, EC50=20 nM), potent δ agonist activity, and excellent opioid receptor selectivity (Ki-µ=32 nM, Ki-κ=37 nM). It also displayed weak inhibitory activity at the hERG channel (IC50= 78 µM). The oral ED50 of c ADL5859 in the FCA mechanical hyperalgesia assay was 1.4 mg/kg. ^[1]
ADL5859 HCl is a promising potential therapeutic agent currently in Phase IIa trials in inflammatory pain, with more Phase II trials planned for 2008. ^[1]