3-O-methyldopa attenuates the effects of Madopar on the haloperidol-induced cataleptic behavior and the locomotor activity in the mouse.
The effects of Madopar (levodopa plus benserazide) on the cataleptic behavioral response to haloperidol and on the locomotor activity in mice were quantitatively compared before and after the administration of 3-O-methyldopa (3OMD). The intraperitoneal administration of 3OMD (200-400 mg/kg) alone did not modify the haloperidol (1.0 mg/kg s.c.)-induced catalepsy. Madopar, depending on the dose regimen, markedly antagonized the haloperidol-induced catalepsy. Pretreatment with 3OMD tended to reverse the antagonistic property of Madopar on the cataleptic behavior in response to haloperidol. The ability of 3OMD to significantly inhibit Madopar effects was observed in the locomotor testing paradigm; the locomotor hyperactivity in Madopar-treated animals was significantly inhibited by a prior intraperitoneal injection of 3OMD. The results from our animal experiments may provide further evidence that impediment of 3OMD formation is meaningful in the treatment of Parkinson's disease with Madopar or levodopa.
Himori
N
N
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Tanaka
Y
Y
Kurasawa
M
M
Mishima
K
K
Akaike
N
N
D000818:Animals; D001545:Benserazide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D004338:Drug Combinations; D006220:Haloperidol / Q000037:antagonists & inhibitors*; D007980:Levodopa / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; D014443:Tyrosine; D007980:Levodopa; D001545:Benserazide; D006220:Haloperidol; C008404:3-methoxytyrosine