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

The aim of the present study was to assess the efficacy of pramipexole (2-a mino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydrochloride), a new dopamine D-2/D-3 receptor agonist, to attenuate parkinsonian-like muscle r igidity in rats. Muscle tone was examined using a combined mechano- and ele ctromyographic (EMG) method, which simultaneously measured the muscle resis tance of a rat's hindlimb to passive extension and flexion at the ankle joi nt, and the EMG activity of the antagonistic muscles of that joint: gastroc nemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg) injected in combination with alpha-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 +alpha-methyl-p-tyrosine- and haloperidol-induced muscle ri gidity. Pramipexole also reduced reserpine-enhanced tonic and reflex EMG ac tivities in the gastrocnemius muscle. The present results suggest that stim ulation of the postsynaptic dopamine receptor may be chiefly responsible fo r the antiparkinsonian action of pramipexole. The ability of pramipexole to diminish the parkinsonian-like muscle rigidity seems to indicate a therape utic value of this compound in the treatment of Parkinson's disease. (C) 19 99 Elsevier Science B.V. All rights reserved.