LONG-TERM DOPAMINERGIC THERAPY OF PARKINSON DISEASE

Abstract

The use of dopaminergic tools, particularly levodopa and dopamine receptors agonists (DRA), for many years allowed to effectively control the major motor symptoms of Parkinson disease, supporting mobility and daily activity, and eventually increasing the survivability of patients. However, a few years after the start of the Levodopa intake the vast majority of patients have motor fluctuations and dyskinesias. The Levodopa action is ensured not only by the short-term but also by the so-called long-term effect of Levodopa, which is developing when the drug is taken regularly. The long-term response provides at least half of the total response  to dopaminergic drugs, particularly, Levodopa. As the disease  progresses, the long-term response  tends to decrease, with a more precise «pulse» of a short-term reaction that does not affect its parameters. It is believed that this is related to the development of the phenomenon of «dose-end exhaustion» and then to «turn on-off». Thus, the task of delaying the occurrence of motor fluctuations must be to keep the long-term dopaminergic effect as long as possible.

Dopaminergic receptors agonists (DRA) are capable of direct stimulating of dopamine receptors on striatal neurons, bypassing degeneration nigrostriatal cells, thus simulating operation of an endogenous mediator.

Agonists of D2-receptors can induce long-term reactions. It is shown that in six weeks after the Ropinirol intake, the subsequent discontinuation of its application results in a slow rise in the motor symptoms during a week. The effectiveness of Ropinirol with the prolonged release at various stages of the PD is confirmed in several placebo-controlled studies. The role of a slow release dosage of Ropinirol in maintaining a long-term response requires special study.