Endothelin has been reported to mediate inflammatory and cancer pain by acting on Endothelin-A (ET-A) receptors. Selective ET-A receptor antagonists have been found to attenuate nociception. Animal studies have demonstrated that ET-A receptor antagonists can potentiate morphine analgesia and prevent the development of tolerance.
PMZ-2123 is an ET-A receptor antagonist that potentiates analgesic effects of morphine and oxycodone, reduces the use of opioids, and maintains adequate pain relief. PMZ-2123 can reverse or avoid the development of opioid tolerance. Patients who have already developed tolerance to opioids can be treated with PMZ-2123 and adequate pain relief can be achieved with a lower dose of opioid.
The development of PMZ-2123 to potentiate analgesic effects of morphine and oxycodone and eliminate tolerance will have a major clinical impact in reducing the use of opioids and maintain adequate pain relief. It will reduce the risk of abuse, misuse, addiction, overdose, and deaths due to prescription opioid analgesics.
PMZ-2123 is in preclinical stage of development.