Venlafaxine, Tramadol and Tapentadol are all opioids. Opioids, generally bind to the mu1 opioid receptor. This receptor is said to be the ‘gateway to addiction’.
Venlafaxine was once thought to be only an SNRI. It is not only an SNRI, it is also an opioid and an NMDA antagotist as well as sharing a chemical backbone with ADHD drugs like Ritalin.
To demonstrate the opioid activity, a protein-ligand docking software suite was used.
Here is the website: http://www.swissdock.ch/docking
Here is how to set up a binding for Desvenlafaxine (venlafaxine’s active metabolite). (‘oprm1’ is the code for the Mu1 Opioid)
This was run for
1) Ciramadol (it is already in its active form)
2) Tapendatol (it is already in its active form)
3) O-desmethyltramadol (active ingredient of Tramadol)
4) Desvenlafaxine (active ingredient of Venlafaxine)
After each docking was run, a program called “Chimera” was used to assemble the 3d models:
https://www.cgl.ucsf.edu/chimera/
Here are the binding sites of the Mu1 Human Opioid Receptor. There are four of them.
(source: https://www.sciencedirect.com/science/article/abs/pii/S1570963916302758)
And now, look for those same 4 binding sites in the following 4 models:
Ciramadol
Tapentadol
Tramadol
Venlafaxine
As you can see in each case, each of the 4 chemicals binds to all 4 binding sites on the Mu1 opioid receptor. Venlafaxine is an opioid.