Re-engineered plant compound reduces morphine-seeking behaviors in mice

Re-engineered plant compound reduces morphine-seeking behaviors in mice

Antiviral compound from banana plants shows potential for clinical use against influenza The team altered vincamine's chemical structure, producing a diverse library of 80 small molecules. They then screened seven of these molecules for the ability to bind to certain protein receptors and block their action. One of the molecules, which they refer to as "V2a," inhibited a protein called hypocretin receptor 2 (HCRTR2) that is involved in heroin dependence, whereas the parent compound, vincamine, had no effect. The researchers then tested this compound in mice, finding that pretreatment with V2a prevented mice from spending extra time in a chamber where morphine is administered. In another experiment, mice that had "recovered" from morphine addiction, and then were treated with V2a, did not relapse to morphine-seeking behaviors in response to stress, unlike mice that were not treated with the new molecule. The team also conducted molecular modeling experiments to visualize how the compound binds to HCRTR2, which could allow them to tweak the structure of the compound for even stronger binding and efficacy . Source: American Chemical Society Journal reference: Norwood, V.M., et al. (2020) Preventing Morphine Seeking Behavior through the Re-engineering of Vincamine’s Biological Activity. Journal of Medicinal Chemistry . doi.org/10.1021/acs.jmedchem.9b01924 .



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