d2-like receptors as the base of multi

D2-LIKE RECEPTORS AS THE BASE OF MULTI-TARGET DIRECTED
LIGANDS FOR THE TREATMENT OF SCHIZOPHRENIA
Stefania Butini
European Research Centre for Drug Discovery and Development (NatSynDrugs), University of Siena, Via Aldo Moro 2, 53100 Siena,
Italy.
Dopamine and its five receptor subtypes are intimately involved in numerous neurological disorders
and in drug addiction and dependence. In particular, the D2-like receptors play a pivotal role in the
regulation of a variety of behaviors, and have been established as valuable pharmacological targets
for the treatment of neurological and psychiatric disorders. Most neurological diseases have a
multifactorial nature and the number of molecular mechanisms ascertained as underpinning these
diseases is continuously evolving. Neurological diseases such as schizophrenia, depression, and
others share a complex origin related to a complicated and intertwined dysregulation of multiple
neurotransmitter systems. In this view, these systems cannot be considered separately; hence the
treatment of these diseases requires the development of drugs displaying a multireceptor affinity
profile including D2-like receptors and a series of other GPCRs, mostly serotoninergic. In this frame,
as a result of our longstanding medicinal chemistry efforts in the field, we gathered considerable
experience in the development of multitarget directed ligands as D2-like receptor antagonists
featuring different extents of D2-like affinity.
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