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Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates.
Mov Disord. 2005 Mar; 20(3):306-14.MD

Abstract

Long-acting dopamine agonist drugs induce a lower incidence of dyskinesia in MPTP-treated primates and patients with Parkinson's disease compared to pulsatile treatment with levodopa, supporting the concept of continuous dopaminergic stimulation as a means of dyskinesia avoidance. We examined the effects of L-dopa administered with or without the COMT inhibitor entacapone on dyskinesia induction in previously untreated MPTP-treated common marmosets. Administration of L-dopa (12.5 mg/kg p.o.) plus carbidopa twice daily produced fluctuating improvement in motor behavior coupled with dyskinesia. Coadministration with entacapone produced similar patterns of motor improvement and dyskinesia that were not different from that produced by L-dopa alone. Treatment with L-dopa (6.25 mg/kg p.o.) plus carbidopa four times daily reversed motor disability and induced dyskinesia in a manner that was not different from the twice-daily treatment regimens. However, coadministration with entacapone produced more continuous improvement in locomotor activity with less dyskinesia than animals treated with L-dopa four times daily alone. These data support the notion that pulsatile stimulation contributes to the development of dyskinesia and suggests that more frequent dosing of L-dopa plus entacapone may be a useful treatment strategy for patients in the early stages of Parkinson's disease.

Authors+Show Affiliations

Neurodegenerative Diseases Research Centre, GKT School of Biomedical Sciences, King's College, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15490461

Citation

Smith, Lance A., et al. "Multiple Small Doses of Levodopa Plus Entacapone Produce Continuous Dopaminergic Stimulation and Reduce Dyskinesia Induction in MPTP-treated Drug-naive Primates." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 20, no. 3, 2005, pp. 306-14.
Smith LA, Jackson MJ, Al-Barghouthy G, et al. Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates. Mov Disord. 2005;20(3):306-14.
Smith, L. A., Jackson, M. J., Al-Barghouthy, G., Rose, S., Kuoppamaki, M., Olanow, W., & Jenner, P. (2005). Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates. Movement Disorders : Official Journal of the Movement Disorder Society, 20(3), 306-14.
Smith LA, et al. Multiple Small Doses of Levodopa Plus Entacapone Produce Continuous Dopaminergic Stimulation and Reduce Dyskinesia Induction in MPTP-treated Drug-naive Primates. Mov Disord. 2005;20(3):306-14. PubMed PMID: 15490461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple small doses of levodopa plus entacapone produce continuous dopaminergic stimulation and reduce dyskinesia induction in MPTP-treated drug-naive primates. AU - Smith,Lance A, AU - Jackson,Michael J, AU - Al-Barghouthy,Ghassan, AU - Rose,Sarah, AU - Kuoppamaki,Mikko, AU - Olanow,Warren, AU - Jenner,Peter, PY - 2004/10/19/pubmed PY - 2005/7/1/medline PY - 2004/10/19/entrez SP - 306 EP - 14 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 20 IS - 3 N2 - Long-acting dopamine agonist drugs induce a lower incidence of dyskinesia in MPTP-treated primates and patients with Parkinson's disease compared to pulsatile treatment with levodopa, supporting the concept of continuous dopaminergic stimulation as a means of dyskinesia avoidance. We examined the effects of L-dopa administered with or without the COMT inhibitor entacapone on dyskinesia induction in previously untreated MPTP-treated common marmosets. Administration of L-dopa (12.5 mg/kg p.o.) plus carbidopa twice daily produced fluctuating improvement in motor behavior coupled with dyskinesia. Coadministration with entacapone produced similar patterns of motor improvement and dyskinesia that were not different from that produced by L-dopa alone. Treatment with L-dopa (6.25 mg/kg p.o.) plus carbidopa four times daily reversed motor disability and induced dyskinesia in a manner that was not different from the twice-daily treatment regimens. However, coadministration with entacapone produced more continuous improvement in locomotor activity with less dyskinesia than animals treated with L-dopa four times daily alone. These data support the notion that pulsatile stimulation contributes to the development of dyskinesia and suggests that more frequent dosing of L-dopa plus entacapone may be a useful treatment strategy for patients in the early stages of Parkinson's disease. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/15490461/Multiple_small_doses_of_levodopa_plus_entacapone_produce_continuous_dopaminergic_stimulation_and_reduce_dyskinesia_induction_in_MPTP_treated_drug_naive_primates_ DB - PRIME DP - Unbound Medicine ER -