Revealing the structure and mechanisms of action of a synthetic opioid with model biological membranes at the air-water interface.

Synthetic opioids such as piperazine derivative called MT-45 interact with opioid receptors in a manner similar to morphine leading to euphoria, a sense of relaxation and pain relief and are commonly used as substituents of natural opioids. In this study we show the changes in the surface properties of nasal mucosa and intestinal epithelial model cell membranes formed at the air - water interface using Langmuir technique upon the exposure to MT-45. Both membranes constitute the first barrier to absorb this substance into the human body. The presence of the piperazine derivative affects the organization of both DPPC and ternary DMPC:DMPE:DMPS monolayers treated as simple models of nasal mucosa and intestinal cell membranes, respectively. This novel psychoactive substance (NPS) leads to the fluidization of the model layers, which may indicate their increased permeability. MT-45 has a greater influence on the ternary monolayers characteristic of the intestinal epithelial cells than nasal mucosa. It might be attributed to the increased attractive interactions between the components of the ternary layer, which in turn increase the interactions with a synthetic opioid. Additionally, the crystal structures of MT-45 determined by single-crystal and powder X-ray diffraction methods allowed us to both provide useful data for facilitating the identification of synthetic opioids as well as to attribute the effect of MT-45 to the ionic interactions between protonated nitrogen atoms and negatively charged parts of the polar heads of the lipids.