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The role of histamine and acetylcholine in cognitive functions suggests that compounds able to increase both histaminergic and cholinergic neurotransmissions in the brain should be considered as promising therapeutic options. For this purpose, dual inhibitors of histamine H3 receptors (H3R) and cholinesterases (ChEs) have been designed and assessed. In this context, this paper reviews the strategies used to obtain dual H3R/ChEs ligands using multitarget design approaches. Hybrid compounds designed by linking tacrine or flavonoid motifs to H3R antagonists were obtained with high affinity for both targets, and compounds designed by merging the H3R antagonist pharmacophore with known anticholinesterase molecules were also reported. These reports strongly suggest that key modifications in the lipophilic region (including a second basic group) seem to be a strategy to reach novel compounds, allied with longer linker groups to a basic region. Some compounds have already demonstrated efficacy in memory models, although the pharmacokinetic and toxicity profile should be considered when designing further compounds. In conclusion, the key features to be considered when designing novel H3R/ChEs inhibitors with improved pharmacological profile were herein summarized. [ABSTRACT FROM AUTHOR]

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The article reviews several books including "Development Success: Historical Accounts From More Advanced Countries," edited by Augustin K. Fosu, "The Oxford Handbook of Food History," edited by Jeffrey M. Pilcher, and "Urban Poverty in the Global South: Scale and Nature," by Diana Mitlin and David Satterthwaite.