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 Parkinson's disease and are able to potentiate the ability of L-DOPA to reverse 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 in several in vivo and in vitro experiments. We now report that in monoamine depleted rats (pretreated with reserpine, 5 mg/kg, and alpha-methyl-para-tyrosine, 250 mg/ kg i.p.) flupirtine dose-dependently (1-20 mg/kg i.p.) suppressed rigidity, measured as tonic EMG activity in the gastrocnemius muscle, but had no effect on akinesia, measured as locomotor 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 relevance, since flupirtine is devoid of the typical side effects of NMDA-receptor antagonists.
Schwarz
M
M
Department of Neurology, Technical University, Aachen, Federal Republic of Germany.
Nolden-Koch
M
M
Purr
J
J
Pergande
G
G
Block
F
F
D000631:Aminopyridines / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D015306:Biogenic Monoamines / Q000378:metabolism*; D004357:Drug Synergism; D004576:Electromyography; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000631:Aminopyridines; D000700:Analgesics; D000978:Antiparkinson Agents; D015306:Biogenic Monoamines; D018696:Neuroprotective Agents; D007980:Levodopa; C034161:flupirtine