Early administration of entacapone prevents levodopa-induced motor fluctuations in hemiparkinsonian rats
Marin C, Aguilar E, Bonastre M, Tolosa E, Obeso JA.
Laboratori de Neurologia Experimental, Servei de Neurologia, Fundació Clínic-Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.
The purpose of this study was to investigate the effect of the catechol-O-methyltransferase (COMT) inhibitor, entacapone, in the reversal and prevention of "wearing-off" phenomena in hemiparkinsonian rats. Catechol-O-methyltransferase (COMT) inhibitors increase the half-life and bioavailability of levodopa, providing more continuous dopamine receptor stimulation.
This raises the possibility of using levodopa and a COMT inhibitor not only to treat motor complications, but also to prevent their development. Male Sprague-Dawley rats received a unilateral 6-hydroxydopamine (6-OHDA) administration in the nigrostriatal pathway. Two sets of experiments were performed.
First, animals were treated with levodopa (50 mg/kg/day with benserazide 12.5 mg/kg/day, twice daily (b.i.d.), intraperitoneally (i.p.) for 22 days. On day 23, animals received either entacapone (30 mg/kg, i.p.) or vehicle with each levodopa dose. In the second set, animals were treated either with levodopa (50 mg/kg/day, i.p.) plus entacapone (30 mg/kg/day, i.p.) or levodopa (50 mg/kg/day, i.p.) plus vehicle, administered two or three times daily [b.i.d. or thrice daily (t.i.d.), respectively] for 22 consecutive days. Entacapone both reversed and prevented the shortening of the motor response duration that defines "wearing-off" motor fluctuations. Entacapone also decreased the frequency of failures to levodopa.
The combination of levodopa and entacapone may reduce the likelihood of motor fluctuation development and may thus become a valuable approach to treat Parkinson disease whenever levodopa is needed.
CITATION Exp Neurol. 2005 Mar;192(1):184-93