Efficacy of pramipexole, a new dopamine receptor agonist, to relieve the parkinsonian-like muscle rigidity in rats

Abstract

The aim of the present study was to assess the efficacy of pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochloride), a new dopamine D 2/D 3 receptor agonist, to attenuate parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic (EMG) method, which simultaneously measured the muscle resistance of a rat's hindlimb to passive extension and flexion at the ankle joint, and the EMG acitivity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg) injected in combination with α-methyl-p-tyrosine (250 mg/kg) or by haloperidol (0.5 mg/kg). Pramipexole in doses of 0.5–5 mg/kg antagonized both reserpine+α-methyl- p-tyrosine- and haloperidol-induced muscle rigidity. Pramipexole also reduced reserpine-enhanced tonic and reflex EMG activities in the gastrocnemius muscle. The present results suggest that stimulation of the postsynaptic dopamine receptor may be chiefly responsible for the antiparkinsonian action of pramipexole. The ability of pramipexole to diminish the parkinsonian-like muscle rigidity seems to indicate a therapeutic value of this compound in the treatment of Parkinson's disease.