Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.

Abstract

The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic method, which simultaneously measured muscle resistance of a rat hindfoot to passive extension and flexion in the ankle joint and the electromyographic (EMG) activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg ip) injected in combination with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg ip). L-DOPA (25 mg/kg ip) or SCH 58261 (0.1 mg/kg ip) administered separately, slightly influenced the reserpine + alpha-MT-induced muscle rigidity. However, only ankle joint extension was affected significantly while the effect on flexion of the rat hindfoot was not significant. Neither L-DOPA nor SCH 58261 given separately modified the reserpine-enhanced tonic or reflex EMG activities in both muscles examined. However, when L-DOPA (25 mg/kg) was given together with SCH 58261 (0.1 mg/kg), a clear synergistic effect was seen on both examined movements and muscles. The present results show that the blockade of adenosine A2A receptors potentiates the antiparkinsonian effect of L-DOPA. Since such an effect was seen in different animal models of Parkinson's disease (PD), it seems that co-administration of SCH 58261 may allow for the lowering of the doses of L-DOPA in clinical practice, which indicates a potential therapeutic value of this compound in the treatment of PD.

• Authors: Jadwiga Wardas
• Journal: Polish journal of pharmacology (Pol J Pharmacol) 2003 Mar-Apr Vol. 55 Issue 2 Pg. 155-64 ISSN: 1230-6002 [Print] Poland
• PMID: 12926542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine
• Adenosine A2 Receptor Antagonists
• Antiparkinson Agents
• Pyrimidines
• Triazoles
• Levodopa
• Reserpine

Topics

• Adenosine A2 Receptor Antagonists
• Animals
• Ankle Joint (drug effects, physiopathology)
• Antiparkinson Agents (pharmacology)
• Disease Models, Animal
• Drug Synergism
• Electromyography
• Levodopa (pharmacology)
• Male
• Muscle Rigidity (chemically induced, drug therapy, physiopathology)
• Muscle, Skeletal (drug effects, physiopathology)
• Pyrimidines (pharmacology)
• Rats
• Rats, Wistar
• Reserpine
• Triazoles (pharmacology)