title: New insight into the therapeutic role of the serotonergic system in Parkinson's disease.
abstract: Parkinson's disease (PD) is a common, late-onset neurodegenerative disorder that shows progressive extrapyramidal motor disorders (e.g., bradykinesia, resting tremors, muscle rigidity and postural instability) and various non-motor symptoms (e.g., cognitive impairment, mood disorders, autonomic dysfunction and sleep disorders). While dopaminergic agents such as L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine D2 agonists are widely used for the treatment of PD, there is still high clinical unmet need for novel medications that overcome the limitations of current therapies. Evidence is now accumulating that the serotonergic nervous system is involved in the pathophysiological basis of PD and can provide benefits in the treatment of PD through its diverse functions. Among 5-HT receptor subtypes, 5-HT1A, 5-HT2, 5-HT3 and 5-HT6 receptors play an important role in modulating extrapyramidal motor disorders. In addition, 5-HT1A, 5-HT2, 5-HT3, 5-HT4 and 5-HT6 receptors are implicated in modulation of cognitive impairment, mood disorders (e.g., depression and anxiety) and/or psychosis, which are frequently observed in patients with PD. Specifically, stimulation of 5-HT1A receptors seems to be effective for multiple PD symptoms including parkinsonism, L-DOPA-induced dyskinesia, cognitive impairment, mood disorders and neurodegeneration of dopamine neurons. Blockade of 5-HT2 receptors is also likely to improve parkinsonism, depressive mood and cognitive impairment. In addition, it was recently demonstrated that 5-HT2A inverse agonists can alleviate PD psychosis. All these findings emphasize the therapeutic roles of the serotonergic system in PD and stimulate new insight into novel treatments by modulating 5-HT1A and 5-HT2 receptors.
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan. Electronic address: yohno@gly.oups.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tokudome
authors.affiliation: Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kunisawa
authors.affiliation: Hiroshima University and Nagisa Clinic, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sasa
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000978:Antiparkinson Agents; D011985:Receptors, Serotonin; D018490:Serotonin Agents
keywords: 5-HT receptors; Clinical unmet needs; Extrapyramidal motor disorders; Non-motor symptoms; Parkinson's disease; Serotonergic system