Excitatory amino acid receptor antagonists lead to marked suppression
of parkinsonian-like symptoms in rodent and primate models of Parkinso
n's disease and are able to potentiate the ability of L-DOPA to revers
e akinesia and ameliorate muscular rigidity displayed in these animal
models. Flupirtine, which is clinically used as a non-opioid analgesic
agent, has some N-methyl-D-aspartate (NMDA) antagonistic properties i
n several in vivo and in vitro experiments. We now report that in mono
amine depleted rats (pretreated with reserpine, 5 mg/kg, and alpha-met
hyl-para-tyrosine, 250 mg/kg i.p.) flupirtine dose-dependently (1-20 m
g/kg i.p.) suppressed rigidity, measured as tonic EMG activity in the
gastrocnemius muscle, but had no effect on akinesia, measured as locom
otor activity. In addition, it potentiated the antiparkinsonian effect
of L-DOPA on akinesia and rigidity in this rodent model of Parkinson'
s disease. These effects of flupirtine are of particular clinical rele
vance, since flupirtine is devoid of the typical side effects of NMDA-
receptor antagonists.