Oxpentifylline in Parkinson's disease
Oxpentifylline is a methylxanthine derivative related to theophylline. This is a widely used group of pharmacological agents of which oxpentifylline is the most recent addition. It has been shown to inhibit phosphodiesterase in a wide variety of tissues8 including brain.9
In addition oxpentifylline has been shown to reduce blood viscosity'0 and to increase red cell flexibility, probably as a result of its effects on cyclic AMP in the red blood cell."
Oxpentifylline is currently used for the treatment of peripheral vascular disease. In view of its potent effect on phosphodiesterase, oxpentifylline was examined in various animal models to see whether it would potentiate the effects of dopaminergic agonists (B Costall and R Naylor, personal communication).
The only situation in which a potentiation was found was in a "denervation animal model" using rats with 6-hydroxydopamine lesions in the striatum and mesolimbic areas. Arbuthnott and his colleagues7 had obtained similar results with aminophylline.
Thirteen patients were included in the trial.
Two patients were withdrawn during the dose titration period on oxpentifylline; one developed severe nausea, and the other complained of nausea and developed dyskinetic movements.
The remaining 11 patients completed the trial and their results are summarised (see table).
Of these patients, two complained of transient nausea which did not persist but no other significant side effects were encountered.
Ten of the 11 patients were able to tolerate the maximum doses of oxpentifylline (1200 mg/day).
This was a small sample of patients and as can be seen the results were variable.
Although some patients were improved by the addition of oxpentifylline to their existing therapy, this followed no clear pattern and was not statistically significant (using the Wilcoxon signed rank test).
However, eight patients experienced abnormal involuntary movements, or a striking worsening of movements if previously present, while on oxpentifylline.
Dyskinetic movements were not altered in patients number 2 and 11 while on the active agent, and patient number 10 showed a reduction in respect to her dyskinesias. The latter was the only patient being treated with bromocriptine during the trial period.