MT-110 (BPN-0027490) is a non-muscle myosin NMIIB -selective inhibitor with high brain penetration and favorable safety profile. MT-110 specifically disrupts NMIIB-dependent actin dynamics in dendritic spines, while it exerts no significant adverse effects on cardiac myosin II and cardiac functions (such as cardiac output and heart rate) at tested concentrations. A single administration of MT-110 produces long-lasting (sustained for several weeks) blockade of methamphetamine motivation associated with environmental cues. MT-110 exhibits extremely high specificity, with no interference with cocaine motivation, hippocampus-dependent memory, fear memory, or locomotor and anxiety-like behaviors. MT-110 serves as a valuable tool compound for investigating the mechanisms of methamphetamine use disorder.
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