Syntrix Discovers Desmetramadol is G-Protein Biased Opioid Receptor Agonist

AUBURN, Wash., Feb. 4, 2020 /PRNewswire/ -- Syntrix Pharmaceuticals announces the discovery that desmetramadol is a G-protein biased opioid receptor agonist.  The results, published in Frontiers in Pharmacology show that desmetramadol, the active metabolite of tramadol, is as effective as morphine, oxycodone and fentanyl in eliciting G protein coupling at the human μ opioid receptor (MOR) involved in pain relief, but surprisingly, supra-therapeutic concentrations typical of overdose spare human MOR-mediated barrestin2 recruitment, the signaling pathway of the receptor thought to mediate lethal opioid-induced respiratory depression.

Tramadol is the second most prescribed opioid in the United States.  It treats moderate to severe pain but lethal respiratory depression is uncommon even in large overdose, making tramadol unique from other opioids.  The reason for this safety property of tramadol has remained elusive but has led tramadol to become an important option in the Opioid Crisis.

Pain relief by tramadol requires metabolism in the body to desmetramadol.  Tramadol metabolism to desmetramadol is abnormal in up to half of patients which results in decreased pain relief and increased side effects.  The FDA  tramadol label warns of its metabolic liabilities.  Syntrix is developing desmetramadol as a strategy to deliver the active metabolite directly and thereby eliminate the metabolic liabilities of tramadol while preserving the same efficacy and safety.  Syntrix reported human clinical trials in The Journal of Pain that demonstrated desmetramadol indeed provided the same pain relief and safety as tramadol but without its metabolic liabilities.

"Our recent discovery that desmetramadol is a potent G-protein biased opioid receptor agonist puts further color on desmetramadol's potential clinical benefits," said John Zebala, MD, PhD, President of Syntrix.  Zebala added, "Desmetramadol is not only a 'better tramadol' because it does not have its metabolic liabilities, its mechanism of biased agonism in common with tramadol may afford desmetramadol the same favorable safety profile as tramadol in overdose.  This could place desmetramadol in a unique and pivotal position to address safer opioid prescribing and the Opioid Crisis in the immediate term."

Syntrix development of desmetramadol was supported by the National Institute on Drug Abuse.

DISCLOSURE NOTICE: This release contains forward-looking information that is based on company management's current beliefs and expectations and are subject to currently unknown information, risks and circumstances. Actual results may vary from what is projected.  Syntrix does not undertake any obligation to publicly update these statements, whether as a result of future events or otherwise.

Contact: Aaron Schuler, PhD, 253-833-8009, x21

SOURCE Syntrix Pharmaceuticals