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Entacapone enhances levodopa‐induced reversal of motor disability in MPTP‐treated common marmosets
Author(s) -
Smith Lance A.,
Gordin Ariel,
Jenner Peter,
Marsden C. David
Publication year - 1997
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.870120616
Subject(s) - entacapone , carbidopa , levodopa , catechol o methyl transferase , chemistry , pharmacology , parkinson's disease , medicine , biochemistry , allele , disease , gene
Oral administration of levodopa (L‐dopa) (2.5–25.0 mg/kg) plus carbidopa (12.5 mg/kg p.o.) to MPTP‐treated common marmosets produced a dose‐related increase in locomotor activity and a corresponding decrease in motor disability. Pretreatment with the peripheral COMT inhibitor entacapone (12.5 mg/kg p.o.) enhanced the intensity and duration of the increase in locomotor activity and the reversal of motor disability produced by a threshold dose of L‐dopa (2.5 mg/kg p.o.) plus carbidopa. By contrast, entacapone pretreatment did not potentiate the increased locomotor activity or reversal of motor disability produced by a near‐maximal dose of L‐dopa (12.5 mg/kg p.o.) plus carbidopa. The effects of entacapone (5.0–25.0 mg/kg p.o.) were dose related, with doses of >12.5 mg/kg tending to produce less potentiation of L‐dopa's effects compared to lower doses. Pretreatment with entacapone (12.5 mg/kg p.o.) without carbidopa caused a short‐lasting enhancement of L‐dopa's (12.5 mg/kg p.o.) action, whereas pretreatment with carbidopa (12.5 mg/kg p.o.) alone had a more dramatic effect. However, pretreatment with both carbidopa and entacapone produced the greatest overall motor response. In conclusion, entacapone enhances the motor response produced by a low threshold dose of L‐dopa plus carbidopa. However, optimization of both the dose of L‐dopa and entacapone appears necessary to obtain the maximal therapeutic response.