CHAPTER 13: 5‐HT_1A Receptors as a Therapeutic Target for Parkinson’s Disease

The serotonergic system plays a crucial role in regulating psychoemotional, sensorimotor and cognitive functions in the central nervous system. Among the serotonergic (5‐HT) receptor subtypes, 5‐HT_1A receptors are implicated in the pathogenesis and treatment of anxiety and depression. In addition, recent research into 5‐HT_1A receptors has revealed new therapeutic roles in the treatment of Parkinson’s disease (PD). Specifically, 5‐HT_1A receptors modulate extrapyramidal motor disorders, L‐DOPA‐induced dyskinesia and cognitive impairment. Thus, full or partial 5‐HT_1A agonists improve core Parkinsonian symptoms associated with dopaminergic deficits, dyskinesia induced by chronic L‐DOPA treatment and mood disturbances (anxiety and depression). In addition, partial 5‐HT_1A agonists or antagonists are expected to be effective against cognitive impairment in patients with PD. These findings encourage the discovery of new 5‐HT_1A receptor ligands, which may improve limitations in efficacy and/or adverse reactions in the current therapy of PD.