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

The aim of the present study was to find out whether blockade of adenosine A(2A) receptors by a selective antagonist, SCH 58261, influenced parkinsoni an-like muscle rigidity. Muscle tone was examined using a combined mechano- and electromyographic method which simultaneously measured muscle resistan ce (MMG) of a rat hindfoot to passive extension and flexion in the ankle jo int and electromyographic activity (EMG) of the antagonistic muscles of tha t joint: gastrocnemius and tibialis anterior. Muscle rigidity produced by r eserpine (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-enhanc ed tonic and reflex EMG activities in both the gastrocnemius and the tibial is 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 do se of SCH 58261 (5 mg/kg) decreased tonic EMG activity enhanced by haloperi dol. 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 t reatment of Parkinson's disease. (C) 2001 Wiley-Liss, Inc.