Buspirone, Parkinson's disease, and the locus ceruleus

Buspirone is a novel anxiolytic whose pharmacological profile differs from that of the benzodiazepines and includes dopaminergic agonist effects. Because of these properties, buspirone's usefulness in the management of idiopathic Parkinson's disease was evaluated in a controlled study of 16 outpatients with stage I-IV disease. At doses of 10 to 60 mg/day, no significant group or individual effects could be discerned on standardized disability, dyskinesia, anxiety, or depression scales. At high dose levels (100 mg/day) however, there was a significant worsening of disability ratings and a decrease in dyskinesia scores; anxiety ratings were also significantly increased. The results indicate that buspirone is well tolerated by parkinsonian patients at conventional antianxiety doses of 10 to 40 mg. Clinical effects of high dose treatment, on the other hand, resemble those associated with a reduction in central dopamine mediated synaptic function. Since buspirone reportedly produces dose-dependent stimulation of norepinephrine containing neurons in the locus ceruleus and behavioral symptoms of such activation were observed, these clinical observations support the concept that central noradrenergic stimulation can adversely affect parkinsonian symptoms.