CR4056 is a first-in-class imidazoline-2 (I2) receptor ligand (agonist profile) with CNS tropism and potent analgesic activity in a broad spectrum of disease-based animal models of pain. In these experimental paradigms, CR4056 emerged as one of the most effective non-opioid analgesics ever described. Accumulating evidence on the function(s) of I2 receptors shows that I2 ligands facilitate the noradrenergic inhibitory (descending) pain pathways with an innovative molecular mechanism, and have a marked opioid-sparing activity.
CR4056 is a small molecule for oral administration. Clinical proof of concept for CR4056 as a safe and effective non-opioid analgesic has been obtained in chronic pain associated with osteoarthritis,with extensive phenotyping of patients who participated in the first exploratory, randomized, placebo-controlled Phase II trial. Potential therapeutic indications for CR4056 in subacute and chronic conditions of various origin span from nociceptive to neuropathic pain.
Four Phase I clinical studies have also been completed to investigate the safety, tolerability, and pharmacokinetics of single and repeated ascending oral doses of CR4056 in healthy subjects, and to explore the drug-drug interaction profile of the compound.
There is a strong rationale and experimental evidence for use of CR4056 as an opioid-sparing drug in multimodal analgesia, for patients with severe pain.