Low-dose dopamine doesn’t affect PD motor symptoms

Last Updated: 2008-02-15 17:29:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) – Low doses of apomorphine do not worsen symptoms in patients with Parkinson disease (PD), thus ruling out subthreshold levels of dopaminergic agents as a cause of the "super-off phenomena" that many PD patients experience.

The super-off state, which involves motor fluctuations below a patient’s normal baseline of motor function, is often "very distressing," Dr. Steven A. Gunzler and associates explain in the February issue of the Archives of Neurology. "Some patients may adjust their PD medications to avoid the super-off state as much as to achieve the on state."

They theorize that presynaptic inhibition of dopaminergic neurotransmission occurring at low blood levels of dopaminergic medication causes the super-off motor state. To test their theory, they conducted a crossover clinical trial of 14 patients with moderately severe PD, with symptom duration of 7 to 28 years.

The subjects were randomized to one of six sequences of sub-threshold apomorphine (IV infusion at 12.5 µg/kg/h for 2 hours then at 25 µg/kg/h for 2 hours), high-dose apomorphine (50 µg/kg/h for 2 hours then at 100 µg/kg/h for 2 hours), or saline.

Parkinsonism was measured by finger and foot tapping rates – the number of times a subject tapped the more affected index finger or foot back and forth between two counters. Tapping rates were recorded every 20 to 30 minutes, beginning at 1 hour prior to each daily infusion, until 2 hours after infusions were completed.

Dr. Gunzler, currently at Case Western Reverse University in Cleveland, Ohio, and his team observed no decline in foot or finger tapping rates during subthreshold apomorphine infusions compared with placebo infusions, although the rates did increase significantly during high-dose infusions of the drug.

"This suggests that a presynaptic or autoreceptor action of dopaminergic agents is not important in more advanced PD and is not an explanation for super-off states," the investigators conclude.

Arch Neurol 2008;65:193-198.