Interaction between dopamine and adenosine A2A receptors as a basis for the treatment of Parkinson's disease

Neurol Sci. 2001 Feb;22(1):71-2. doi: 10.1007/s100720170052.

Abstract

The adenosine A2A receptor antagonist SCH 58261 increases the turning behaviour induced by L-dopa in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. In this study we have evaluated the effect of a chronic intermittent administration of L-dopa or SCH 58261 plus L-dopa on turning behaviour. Chronic intermittent administration of SCH 58261 plus L-dopa produced a stable turning behaviour during the course of the treatment, whereas L-dopa alone produced a progressive increase in turning behaviour. Moreover, repeated administration of SCH 58261 failed to produce tolerance to its ability to potentiate L-dopa-induced turning behaviour. The results indicate that SCH 58261 is effective after chronic administration and suggest that SCH 58261 plus L-dopa, differently from Ldopa alone, does not produce alterations in motor responses during the course of the treatment.

MeSH terms

  • Animals
  • Antiparkinson Agents / pharmacology*
  • Denervation
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Interactions / physiology
  • Drug Therapy, Combination
  • Drug Tolerance / physiology
  • Levodopa / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Neostriatum / physiopathology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Neuroprotective Agents / pharmacology*
  • Oxidopamine / pharmacology
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / physiopathology
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / metabolism*
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Substantia Nigra / physiopathology
  • Sympatholytics / pharmacology
  • Triazoles / pharmacology*

Substances

  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Antiparkinson Agents
  • Neuroprotective Agents
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • Sympatholytics
  • Triazoles
  • Levodopa
  • Oxidopamine
  • Dopamine