SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats

Synapse. 2001 Aug;41(2):160-71. doi: 10.1002/syn.1070.

Abstract

The aim of the present study was to find out whether blockade of adenosine A(2A) receptors by a selective antagonist, SCH 58261, influenced parkinsonian-like muscle rigidity. Muscle tone was examined using a combined mechano- and electromyographic method which simultaneously measured muscle resistance (MMG) of a rat hindfoot to passive extension and flexion in the ankle joint and electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity produced by reserpine (5 mg/kg + alpha-methyl-p-tyrosine, 250 mg/kg) was antagonized by SCH 58261 (0.1-5 mg/kg). SCH 58261 (5 mg/kg) also reduced reserpine-enhanced tonic and reflex EMG activities in both the gastrocnemius and the tibialis muscles. Moreover, SCH 58261 in doses of 1 and 5 mg/kg abolished muscle resistance induced by haloperidol (0.5 mg/kg). However, only the highest dose of SCH 58261 (5 mg/kg) decreased tonic EMG activity enhanced by haloperidol. Administration of L-DOPA (75 and 100 mg/kg) dose-dependently decreased the muscle resistance as well as tonic EMG activity evoked by haloperidol. Combined administration of SCH 58261 (0.1 mg/kg) and L-DOPA (50 mg/kg) in doses which did not affect the haloperidol-induced muscle rigidity produced a pronounced synergistic effect. The ability of SCH 58261 to diminish the parkinsonian-like muscle rigidity and to potentiate the effect of L-DOPA in this model seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology
  • Animals
  • Ankle Joint / drug effects
  • Ankle Joint / physiology
  • Dopamine Agents / pharmacology
  • Dopamine Antagonists / pharmacology
  • Drug Combinations
  • Electromyography
  • Haloperidol / pharmacology
  • Levodopa / pharmacology
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle Rigidity / chemically induced
  • Muscle Rigidity / drug therapy*
  • Muscle Rigidity / physiopathology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiopathology
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Neostriatum / physiopathology
  • Neuroprotective Agents / pharmacology*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology
  • Purinergic P1 Receptor Antagonists*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1 / metabolism*
  • Reserpine / pharmacology
  • Triazoles / pharmacology*

Substances

  • 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
  • Adrenergic Uptake Inhibitors
  • Dopamine Agents
  • Dopamine Antagonists
  • Drug Combinations
  • Neuroprotective Agents
  • Purinergic P1 Receptor Antagonists
  • Pyrimidines
  • Receptor, Adenosine A2A
  • Receptors, Purinergic P1
  • Triazoles
  • Levodopa
  • Reserpine
  • Haloperidol