Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys

Exp Neurol. 2000 Apr;162(2):321-7. doi: 10.1006/exnr.2000.7350.


The novel selective adenosine A(2A) receptor antagonist KW-6002 improves motor disability in MPTP-treated parkinsonian marmosets without provoking dyskinesia. In this study we have investigated whether KW-6002 in combination with l-DOPA or selective D1 or D2 dopamine receptor agonists enhances antiparkinsonian activity in MPTP-treated common marmosets. Combination of KW-6002 with the selective dopamine D2 receptor agonist quinpirole or the D1 receptor agonist SKF80723 produced an additive improvement in motor disability. Coadministration of KW-6002 with a low dose of L-DOPA also produced an additive improvement in motor disability, and increased locomotor activity. The ability of KW-6002 to enhance antiparkinsonian activity was more marked with L-DOPA and quinpirole than with the D1 agonist. However, despite producing an enhanced antiparkinsonian response KW-6002 did not exacerbate L-DOPA-induced dyskinesia in MPTP-treated common marmosets previously primed to exhibit dyskinesia by prior exposure to L-DOPA. Selective adenosine A(2A) receptor antagonists, such as KW-6002, may be one means of reducing the dosage of L-DOPA used in treating Parkinson's disease and are potentially a novel approach to treating the illness both as monotherapy and in combination with dopaminergic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Administration, Oral
  • Animals
  • Callithrix
  • Carbidopa / administration & dosage
  • Disease Models, Animal
  • Drug Synergism
  • Drug Therapy, Combination
  • Dyskinesia, Drug-Induced / therapy*
  • Female
  • Injections, Intraperitoneal
  • Levodopa / administration & dosage*
  • Levodopa / adverse effects
  • Male
  • Motor Activity / drug effects
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / physiopathology
  • Purinergic P1 Receptor Antagonists*
  • Purines / administration & dosage*
  • Quinpirole / administration & dosage*
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D1 / agonists*
  • Receptors, Dopamine D2 / agonists


  • Purinergic P1 Receptor Antagonists
  • Purines
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Quinpirole
  • istradefylline
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Carbidopa