Opioid Receptors

Developing novel Opioids

Opioids are treatment of choice for moderate to severe pain providing excellent pain relief in most patients. Since its isolation from opium more than 200 years ago, morphine remains the most widely used analgesic.

Classical opioids like morphine exert their pharmacological activity by interacting with the µ-opioid receptor (MOR).

However, besides their analgesic action classical opioids induce various side effects.

The most dangerous and potentially life threatening one is respiratory depression. More common side effects are e.g. sedation, nausea and vomiting, constipation, and urinary retention. Finally, classical opioids are associated with development of tolerance, physical dependence, and positive reinforcing properties.

Grünenthal is actively developing novel, centrally acting analgesics with combined mode of action - µ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI). Activation of the MOR agonism and inhibition of noradrenaline reuptake are both well recognized as analgesic principles in acute and chronic pain indications.

The novel compounds are potent analgesics with an improved tolerability profile and therefore less side effects, as compared with classical opioids.

In addition to the µ-opioid receptor (MOR) the opioid receptor family comprises, three other receptor classes: δ-opioid receptors (DOR), κ-opioid receptors (KOR), and the recently identified opioid-receptor-like receptors (ORL1).

Grünenthal is actively developing novel opioids with affinity to multiple opioid receptor classes, especially MOR, DOR, and ORL1. These novel compounds combine high efficacy in the treatment of moderate to severe pain with a significantly improved side-effect profile compared to classical opioids.