ANTIPARKINSONIAN EFFECT OF FLUPIRTINE IN MONOAMINE-DEPLETED RATS

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.