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SCH 58261, an A 2A adenosine receptor antagonist, counteracts parkinsonian‐like muscle rigidity in rats
Author(s) -
Wardas Jadwiga,
Konieczny Jolanta,
LorencKoci Elżbieta
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.1070
Subject(s) - endocrinology , medicine , haloperidol , antagonist , chemistry , adenosine , pharmacology , anesthesia , receptor , dopamine
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 + α‐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. Synapse 41:160–171, 2001. © 2001 Wiley‐Liss, Inc.