Entacapone enhances levodopa-induced reversal of motor disability in MPTP-treated common marmosets.
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.
Smith
L A
LA
Neurodegenerative Diseases Research Centre, King's College, London, England, U.K.
Gordin
A
A
Jenner
P
P
Marsden
C D
CD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D000818:Animals; D002144:Callithrix; D002230:Carbidopa / Q000627:therapeutic use; D002396:Catechols / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology*; D009570:Nitriles; D012720:Severity of Illness Index
D002396:Catechols; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D009570:Nitriles; D007980:Levodopa; C071192:entacapone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002230:Carbidopa