The administration of L-dopa, a dopamine precursor (i.e. which triggers dopamine production), in the treatment of Parkinson's disease has an undoubtedly beneficial effect in the short term. Unfortunately, it has a sort of boomerang action after prolonged administration (generally five to ten years) in the form of a worsening of motor symptoms called "motor fluctuations".

The most frequent of these fluctuations may be medicinal dyskinesias which, in Parkinson's disease, often take the form of contorsions of the limbs and the trunk. These tend to occur at mid dose when the concentration of the drug in the plasma is at the highest, but may also appear at the beginning or end of a dose.

Another type of motor fluctuation is the "on-off phenomenon", which occurs regardless of the time at which the drug is taken. The patient suddenly "freezes", his/her muscles becoming rigid and his/her movements slowing down. After a period lasting a few seconds or as much as several minutes, (s)he becomes mobile again.

Patients may also experience "off phenomena" at the end of a dose. The effectiveness of L-dopa progressively decreases with the advancement of the disease : patients experience muscular stiffness and freezing with increasing frequency. These symptoms may be alleviated by the administration of a different dose of the drug. In this case, the interval between drug intakes must often be reduced and/or associated with a metabolism inhibitor without the daily dosage necessarily having to be increased.

Motor fluctuations are believed to be due to the fact that, given the progressive loss of dopaminergic neurons, the amount of exogenous dopamine obtained from its precursor (L-dopa) exceeds the storage capacity of the remaining synaptic vesicles. The excess dopamine would then be immediately released into the synaptic cleft, thereby building up a surplus which would lead to the appearance of the symptoms.