Antihistamines H3R/H4R as procognitive agents: a multitarget approach

Abstract

Aging is generally associated with a certain cognitive decline. Although individual differences exist, the mechanisms underlying learning and memory processes are complex and commonly explored in the search for targets to drug therapy. Certain pathological conditions, such as Alzehimer's and Parkinson's diseases, vascular dementia and mood and affective disorders affect cognition. Considering this, the search for new molecules capable to improve the cognitive processes, sometimes known as nootropic agents, is constantly on the focus of pharmaceutical companies as well as in academic research. The role of histaminergic, cholinergic and dopaminergic systems, in addition to increased cerebral blood flow, is widely known and can be considered among the main targets for new drugs. Moreover, it is proposed these conditions are better treated through a multitarget approach, i.e. by affecting more than one target in the same time. With this regards, the present project aims to synthesize and evaluate the activity of a set of dihydrobenzofuranyl-piperazines in in vitro assays in vessels and in the respective receptors, and to the more promising compounds, in cognition models in vivo. The compounds will be prepared mainly by methodologies developed in our group, which usually give good yields. It is expected the set designed can bring some information of SAR that can be valuable to optimize the activity of new compounds in each target, as well as in a multitarget approach. (AU)