O-desmethyltramadol (Omnitram): Proprietary and elegant solution to common pain therapy failure

Unmet Clinical Need

Tramadol is a popular pain medication prescribed over 40 million times each year in the United States for moderate to severe acute, chronic and neuropathic pain.  Tramadol is believed to be safer and less addictive than schedule II opioids such as oxycodone and tapentadol [1], and its use has increased significantly.  Tragically, millions of patients do not obtain pain relief from tramadol because they are unable to metabolize the drug to its active form.  In some patient populations, 1 in 3 patients will not obtain adequate pain relief from tramadol [2].  The need to switch non-responders to schedule II opioids increases the risk of developing addiction and adds costs and inconvenience.  Still other patients metabolize tramadol too quickly, causing rare but life-threatening side effects that include respiratory depression.  There is therefore a critical need for a new tramadol-like pain medication that is effective without requiring metabolism, but that enjoys the same safety and lower addictive potential as tramadol.

Omnitram is Developed

To meet this critical need, Syntrix developed Omnitram, a proprietary solution to tramadol failure that provides the body with the primary active metabolite of tramadol, O-desmethyltramadol, in a precise timed delivery without requiring metabolic activation. Pain relief using Omnitram results from a dual mechanism involving mu-opioid receptor activation and inhibition of the reuptake of norepinephrine (see below).


When Syntrix initially began its program to create a new and improved tramadol-like pain medication, it unexpectedly discovered that it was impossible to simply administer the active metabolite of tramadol directly; doing so resulted in rapid clearance of the molecule and wide variation in blood levels. Overcoming this setback required Syntrix go back to the drawing board. For over a year company scientists tirelessly dedicated themselves to finding a way to correctly deliver the active metabolite to resistant patients. After countless formulations and thousands of samples tested, Omnitram was finally born.

Omnitram is a novel innovative formula that succeeds in releasing the active metabolite in a precise temporal formula that tricks the drug into adopting a blood profile that matches the active metabolite profile from tramadol (see below).


Omnitram is remarkable in that it replicates blood levels of the active tramadol metabolite but without requiring metabolism, thus providing pain relief in patients who would otherwise fail to obtain pain relief from tramadol, as well as preventing dangerously high blood levels of the active metabolite in patients whose genetic make-up causes them to metabolize tramadol excessively fast.

The Omnitram Market

The global market for Omnitram is over $2 billion.  Omnitram targets the existing world opioid and tramadol markets with a “better” tramadol.  Retail U.S. sales of just the generic forms of hydrocodone, oxycodone, fentanyl and tramadol total over $6.1 billion.  Tramadol itself is widely prescribed, with over 40 million prescriptions in the U.S. alone.  Globally, tramadol sales are well over $2.0 billion.  Omnitram's dual mechanism of pain relief is expected to be effective in treating neuropathic pain, a type of pain that is particularly difficult to treat with current therapies.  Opioids are frequently ineffective and other treatments such as gabapentin (Neurontin™) are associated with significant side effects.  No current single drug treatment is effective in more than half of patients, and therefore novel therapeutic approaches are urgently needed. Approximately 26 million patients are affected worldwide and the global market for neuropathic pain is projected to reach $18 billion by 2020.

[1] Tsutaoka BT, Ho RY, Fung SM and Kearney TE.  Comparative toxicity of tapentadol and tramadol utilizing data reported to the National Poison Data System [of the American Association of Poison Control Centers]. Annals of Pharmacotherapy 2015 Sep 14; pii: 1060028015604631. [Epub ahead of print]

[2] Preskorn SH, Kane CP, Lobello K, Nichols AI, Fayyad R, Buckley G, Focht K, and Guico-Pabia CJ.  Cytochrome P450 2D6 phenoconversion is common in patients being treated for depression: Implications for personalized medicine. J Clin Psychiatry 2013 Jun; 74(6):614-21

Acute vs. Chronic Pain

Nociceptive vs. Neuropathic Pain

Transmission of nociceptive pain to the brain and its regulation in the spinal cord via supraspinal pathways that release natural opioids and increase spinal norepinephrine.

Omnitram operates to suppress pain by mimicking endogenous opioid substances at mu-opioid receptors located throughout the pain modulatory system, and augmenting levels of norepinephrine in the spinal cord by blocking its reuptake.