[Is the inhibition of adenosine A(2A) receptors an efficient way of Parkinson's disease treatment?].
The authors intended to focus the attention of the medical community on the potential therapeutic usefulness of A(2A) adenosine receptors antagonists in the treatment of Parkinson's disease. Basal ganglia express a big amount of A(2A) adenosine receptors, occurring mainly on the external surfaces of neurons located at indirect pathways between the striatum, globus pallidus and substantia nigra. Experiments with the animal models of Parkinson's disease indicate that A(2A) receptors are strongly involved in the regulation of the central movement system. Co-localization of A(2A) and dopaminergic D2 receptors in the striatum creates a milieu for an antagonistic interaction between adenosine and dopamine. The experimental data prove that the best mobility improvement of patients with Parkinson's disease could be achieved with a simultaneous activation of dopaminergic D2 receptors and inhibition of adenosine A(2A) receptors. In animal models of Parkinson's disease, the use of selective antagonists of A(2A) receptors, such as istradefylline, led to the reversibility of movement dysfunction. These compounds might improve the mobility during both monotherapy and co-administration with L-dopa and the dopamine receptor agonists. The use of these antagonists in the combined therapy enables the reduction of the L-dopa doses, as well as reduction of the side effects. In the adjunctive therapy, the A(2A) antagonists might be used in both moderate and advanced stages of Parkinson's disease. The long-lasting administration of the A(2A) receptor antagonists does not decrease patient's response and does not cause side effects typical of the L-dopa therapy. It was proved on different animal models that inhibition of A(2A) receptors not only decreases the movement disturbance, but also reveals the neuroprotective activity, which might slow down or stop the progress of the disease.
Ceiślak
Marek
M
Oddział Neurologiczny, Wojewódzki Szpital Zespolony w Toruniu, Toruń. marcies@autograf.pl
Komoszyński
Michał
M
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010300:Parkinson Disease / Q000188:drug therapy*
D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D007980:Levodopa