pharmazz

Opiod Tolerance

Endothelin-A receptor antagonists such as PMZ-2123 potentiate analgesic effects of morphine and oxycodone. Reduces the use of opioids and maintains adequate pain relief. PMZ-2123 has the ability to eliminate and reverse opioid tolerance, patients who have already developed tolerance to opioids can be treated with PMZ-2123 and achieve adequate pain relief with lower doses of opioids.

The development of PMZ-2123 to potentiate analgesic effects of morphine and oxycodone and eliminate tolerance will have 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.

Patents issued in United States.

Status of Opioid Tolerance & Pain Management

Product
Pre-Clinical
Clinical

phase 1

phase 2

phase 3

market

Opioid Tolerance & Pain Management

..

Publications

  • Gulati, S., Briyal, S., Jones, S., Bhalla, S., and Gulati, A. (2017) Attenuation of opioid tolerance by ETB receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice. Heliyon 3, e00317
    Read more
  • Bhalla, S., Andurkar, S. V., and Gulati, A. (2016) Neurobiology of opioid withdrawal: Role of the endothelin system. Life Sci 159, 34-42
    Read more
  • Devarapalli, M., Leonard, M., Briyal, S., Stefanov, G., Puppala, B. L., Schweig, L., and Gulati, A. (2016) Prenatal Oxycodone Exposure Alters CNS Endothelin Receptor Expression in Neonatal Rats. Drug Res (Stuttg) 66, 246-250
    Read more
  • Bhalla, S., Pais, G., Tapia, M., and Gulati, A. (2015) Endothelin ETA receptor antagonist reverses naloxone-precipitated opioid withdrawal in mice. Can J Physiol Pharmacol 93, 935-944
    Read more
  • Bhalla, S., Zhang, Z., Patterson, N., and Gulati, A. (2010) Effect of endothelin-A receptor antagonist on mu, delta and kappa opioid receptor-mediated antinociception in mice. Eur J Pharmacol 635, 62-71
    Read more
  • Gulati, A., Bhalla, S., Matwyshyn, G., Zhang, Z., and Andurkar, S. V. (2009) Determination of adrenergic and imidazoline receptor involvement in augmentation of morphine and oxycodone analgesia by clonidine and BMS182874. Pharmacology 83, 45-58
    Read more
  • Matwyshyn, G. A., Bhalla, S., and Gulati, A. (2006) Endothelin ETA receptor blockade potentiates morphine analgesia but does not affect gastrointestinal transit in mice. Eur J Pharmacol 543, 48-53
    Read more
  • Puppala, B. L., Bhalla, S., Matwyshyn, G., and Gulati, A. (2006) Involvement of central endothelin receptors in neonatal morphine withdrawal. Exp Biol Med (Maywood) 231, 1157-1160
    Read more
  • Bhalla, S., Ciaccio, N., Wang, Z. J., and Gulati, A. (2006) Involvement of endothelin in morphine tolerance in neuroblastoma (SH-SY5Y) cells. Exp Biol Med (Maywood) 231, 1152-1156
    Read more
  • Puppala, B. L., Bhalla, S., Matwyshyn, G., and Gulati, A. (2006) Role of endothelin (ETA) receptors in neonatal morphine withdrawal. Peptides 27, 1514-1519
    Read more
  • Bhalla, S., Matwyshyn, G., and Gulati, A. (2005) Morphine tolerance does not develop in mice treated with endothelin-A receptor antagonists. Brain Res 1064, 126-135
    Read more
  • Puppala, B. L., Matwyshyn, G., Bhalla, S., and Gulati, A. (2004) Role of endothelin in neonatal morphine tolerance. J Cardiovasc Pharmacol 44 Suppl 1, S383-385
    Read more
  • Gulati, A., Bhalla, S., and Matwyshyn, G. (2004) A novel combination of opiates and endothelin antagonists to manage pain without any tolerance development. J Cardiovasc Pharmacol 44 Suppl 1, S129-131
    Read more
  • Puppala, B. L., Matwyshyn, G., Bhalla, S., and Gulati, A. (2004) Evidence that morphine tolerance may be regulated by endothelin in the neonatal rat. Biol Neonate 86, 138-144
    Read more
  • Bhalla, S., Matwyshyn, G., and Gulati, A. (2004) Central endothelin-B receptor stimulation does not affect morphine analgesia in rats. Pharmacology 72, 20-25
    Read more
  • Bhalla, S., Matwyshyn, G., and Gulati, A. (2002) Potentiation of morphine analgesia by BQ123, an endothelin antagonist. Peptides 23, 1837-1845
    Read more
  • Bhalla, S., Matwyshyn, G., and Gulati, A. (2003) Endothelin receptor antagonists restore morphine analgesia in morphine tolerant rats. Peptides 24, 553-56
    Read more