Philip S. Portoghese

Since joining the College of Pharmacy faculty in 1961, Distinguished Professor Philip S. Portoghese, Ph.D., has made significant contributions to the field of medicinal chemistry. His research focuses on the neurosciences, and has been critical to the understanding of pain management, addiction, and tolerance to morphine-like pain relievers. He is recognized around the world for his discoveries related to opioid receptors.

Recently, he developed two new compounds that show promise as a breakthrough drug for treating chronic pain.

Many diseases or traumatic conditions are accompanied by inflammation that may lead to increased sensitivity to pain. Generally, the greater sensitivity is due to release of endogenous substances that make
nerves that carry pain more sensitive. However, the opioid analgesics commonly prescribed today were originally evaluated on normal, non-inflamed animal models.

Analgesics such as morphine, codeine, oxymorphone, oxycodone are generally effective analgesics for short term relief of pain. However, their efficacy usually declines upon chronic use due to tolerance.

“In an effort to develop medications that are effective for the pharmacotherapy of chronic pain without tolerance, we designed two compounds — MMG22 and MCC22 — that inhibit the action of inflammation-induced release of endogenous mediators that would promote pain sensitization of neurons while simultaneously stimulating opioid receptors in neurons,” said Portoghese.

Both MMG22 and MCC22 have analgesic activity equivalent to morphine in normal mice, but their potency becomes greatly amplified in inflamed mice. Additionally, no tolerance is evident for either of the
compounds.

“In a chronic bone cancer mouse model, MMG22 was 3.6-million times greater than morphine,” said Portoghese. “MCC22 was found to be highly effective in the treatment of chronic pain resulting from chemotherapy-induced neuropathy and sickle cell disease.”