Developing novel Analgesics
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 MOR and inhibition of noradrenaline reuptake are both well recognized 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 two other classical receptor subclasses: δ-opioid receptors (DOR) and κ-opioid receptors (KOR). Recently, the Nociceptin/Orphanin FQ Peptide receptor (NOP receptor) has been described as the fourth member of the opioid receptor family. Although, it shares a high level of molecular and functional homology with the classical opioid receptors, from a pharmacological perspective the NOP receptor is regarded as a non-opioid branch of the opioid receptor family.
Grünenthal is actively developing novel analgesics targeting classical opioid receptors, especially MOR and DOR, as well the NOP receptor. 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.