HRH3 and amnesia: Importantly, the memory-enhancing effect observed for E159 was dose-dependent, since the improvement of memory provided by E159 (2.5 mg/kg) in the DIZ-induced amnesia model was significantly higher when compared to the higher doses (5 and 10 mg/kg), demonstrating that an optimum in memory-enhancing effect was observed when the H3R antagonist/inverse agonist E159 was applied at the lowest dose (2.5 mg/kg), and an off-target effect for E159 at higher doses (5 and 10 mg/kg) might have been observed in the current study (Figure 2).