A rapid and excessive increase in extracellular
dopamine(DA) after
L-DOPA administration is considered one of the major causes for
L-DOPA-induced peak-dose
dyskinesia. Therefore, inhibition of excessive rise in
L-DOPA-derived DA is likely to be an ideal treatment for
L-DOPA-induced
dyskinesia. Based on our previous experimental studies that
8-OH-DPAT, a potent
5-HT1A agonist, attenuates an increase in
L-DOPA-induced extracellular DA in the striatum of the rat model of
Parkinson's disease, we hypothesized that
L-DOPA-induced
dyskinesia in patients with
Parkinson's disease is alleviated by a
5-HT1A agonist. In the present study, we administered
tandospirone citrate, a selective
5-HT1A agonist, to patients with
Parkinson's disease suffering from
L-DOPA-induced
dyskinesia.
Tandospirone(15-60 mg/day) was administered to 10 patients with
L-DOPA-induced peak-dose
dyskinesia. Twelve weeks after
tandospirone treatment, duration of
dyskinesia, subjective and objective severity of
dyskinesia, and parkinsonian features were evaluated. Severity of
dyskinesia was decreased in 5 patients; among these, 3 patients experienced slight worsening of parkinsonian features. Four patients showed no change in
dyskinesia; among these, 2 patients showed worsening of parkinsonian features. One patient had slight worsening of
dyskinesia without any change in parkinsonian features. The present study demonstrated that
tandospirone is effective in alleviating
L-DOPA-induced
dyskinesia in 50% of the patients. However, at the same time 50% patients showed slight worsening of parkinsonian features. Both the anti-dyskinetic effect and the worsening of parkinsonian features are thought to be induced by
tandospirone's potent 5-HT1A agonistic activity. Diverse effect of
tandospirone may be caused by its partial agonist activity on 5-HT1A receptors, or may indicate that other causes for the expression of
dyskinesia exist apart from excessive rise in brain DA levels. Administration of a
5-HT1A agonist is a choice for patients with
dyskinesia if the care is taken so as not to induce worsening of parkinsonian features. Further studies such as double-blind trials are needed to confirm the usefulness of a
5-HT1A agonist for
L-DOPA-induced
dyskinesia.