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Pulsatile stimulation of dopamine receptors and levodopa-induced motor complications in Parkinson's disease: implications for the early use of COMT inhibitors.
Neurology. 2000; 55(11 Suppl 4):S72-7; discussion S78-81.Neur

Abstract

Increasing laboratory and clinical evidence indicates that pulsatile stimulation of dopamine receptors contributes to the development of levodopa-related motor complications in PD. In keeping with this concept, clinical trials have demonstrated that initiating therapy with a long-acting dopamine agonist reduces the risk of inducing motor complications in comparison to levodopa. However, the introduction of levodopa is associated with the development of motor complications even in the presence of a long-acting dopamine agonist in both PD patients or MPTP treated monkeys. Administration of levodopa with a catechol-O-methyl transferase (COMT) inhibitor increases its plasma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. We hypothesize that the risk of developing motor complications in PD patients when levodopa is introduced can be reduced if the levodopa is coupled with a COMT inhibitor so as to provide more continuous dopaminergic stimulation of dopamine receptors. A proposed algorithm for the treatment of the early PD patient is to initiate therapy with a dopamine agonist, and supplement with levodopa coupled with a COMT inhibitor when the dopamine agonist cannot provide satisfactory clinical benefits.

Authors+Show Affiliations

Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

11147513

Citation

Olanow, C W., and J A. Obeso. "Pulsatile Stimulation of Dopamine Receptors and Levodopa-induced Motor Complications in Parkinson's Disease: Implications for the Early Use of COMT Inhibitors." Neurology, vol. 55, no. 11 Suppl 4, 2000, pp. S72-7; discussion S78-81.
Olanow CW, Obeso JA. Pulsatile stimulation of dopamine receptors and levodopa-induced motor complications in Parkinson's disease: implications for the early use of COMT inhibitors. Neurology. 2000;55(11 Suppl 4):S72-7; discussion S78-81.
Olanow, C. W., & Obeso, J. A. (2000). Pulsatile stimulation of dopamine receptors and levodopa-induced motor complications in Parkinson's disease: implications for the early use of COMT inhibitors. Neurology, 55(11 Suppl 4), S72-7; discussion S78-81.
Olanow CW, Obeso JA. Pulsatile Stimulation of Dopamine Receptors and Levodopa-induced Motor Complications in Parkinson's Disease: Implications for the Early Use of COMT Inhibitors. Neurology. 2000;55(11 Suppl 4):S72-7; discussion S78-81. PubMed PMID: 11147513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pulsatile stimulation of dopamine receptors and levodopa-induced motor complications in Parkinson's disease: implications for the early use of COMT inhibitors. AU - Olanow,C W, AU - Obeso,J A, PY - 2001/1/9/pubmed PY - 2001/2/28/medline PY - 2001/1/9/entrez SP - S72-7; discussion S78-81 JF - Neurology JO - Neurology VL - 55 IS - 11 Suppl 4 N2 - Increasing laboratory and clinical evidence indicates that pulsatile stimulation of dopamine receptors contributes to the development of levodopa-related motor complications in PD. In keeping with this concept, clinical trials have demonstrated that initiating therapy with a long-acting dopamine agonist reduces the risk of inducing motor complications in comparison to levodopa. However, the introduction of levodopa is associated with the development of motor complications even in the presence of a long-acting dopamine agonist in both PD patients or MPTP treated monkeys. Administration of levodopa with a catechol-O-methyl transferase (COMT) inhibitor increases its plasma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. We hypothesize that the risk of developing motor complications in PD patients when levodopa is introduced can be reduced if the levodopa is coupled with a COMT inhibitor so as to provide more continuous dopaminergic stimulation of dopamine receptors. A proposed algorithm for the treatment of the early PD patient is to initiate therapy with a dopamine agonist, and supplement with levodopa coupled with a COMT inhibitor when the dopamine agonist cannot provide satisfactory clinical benefits. SN - 0028-3878 UR - https://www.unboundmedicine.com/medline/citation/11147513/Pulsatile_stimulation_of_dopamine_receptors_and_levodopa_induced_motor_complications_in_Parkinson's_disease:_implications_for_the_early_use_of_COMT_inhibitors_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11147513.ui DB - PRIME DP - Unbound Medicine ER -