Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats.
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.
Wardas
Jadwiga
J
Department of Neurosychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. wardas@if-pan.krakow.pl
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000503:physiopathology; D000978:Antiparkinson Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004576:Electromyography; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine; D014230:Triazoles / Q000494:pharmacology*
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058917:Adenosine A2 Receptor Antagonists; D000978:Antiparkinson Agents; D011743:Pyrimidines; D014230:Triazoles; D007980:Levodopa; D012110:Reserpine