The COMT inhibitor tolcapone potentiates the anticataleptic effect of Madopar in MPP+-lesioned mice |
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Authors: | N. Himori K. Mishima |
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Affiliation: | (1) Department of Pharmacology, Nippon Roche Research Center, 200 Kajiwara, 247 Kamakura, Japan |
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Abstract: | Orally administered Madopar (levodopa/benserazide 41) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP+-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD. |
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Keywords: | Catalepsy Madopar tolcapone 3-O-methyldopa |
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