Improving the Treatment of Parkinson's Disease: A Novel Approach by Modulating 5-HT(1A) Receptors.

Parkinson's disease, the most common neurological disorder in the elderly, is characterized by progressive extrapyramidal motor dysfunction including resting tremors, muscle rigidity, hypolocomotion (bradykinesia and akinesia) and postural instability. Various non-motor features are also seen such as cognitive impairments (deficits in learning and memory) and mood disorders (depression and anxiety). While the 5-HT(1A) receptor has long been implicated in the pathogenesis and treatment of anxiety and depression, recent research has revealed new therapeutic roles for 5-HT(1A) receptors in the treatment of Parkinson's disease. These include the modulation of parkinsonian motor symptoms, L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, cognitive impairments and emesis. Thus, 5-HT(1A) agonists improve the various motor disorders associated with dopaminergic deficits, dyskinesia induced by chronic L-DOPA treatment, mood disturbances (anxiety and depression) and dopamine agonist-induced emesis. In addition, partial 5-HT(1A) agonists are expected to improve cognitive impairment in Parkinson's patients. These findings encourage research into new 5-HT(1A) receptor ligands, which will improve efficacy and/or ameliorate adverse reactions in the treatment of Parkinson's disease.