title: Clinical implications of sustained dopaminergic stimulation.
abstract: Fluctuations in motor performance are the major problems in chronic management of Parkinson's disease. Most of these fluctuations reflect the decline of levodopa availability. As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened. The postsynaptic dopamine receptors at this point are exposed to a nonphysiologic shift in dopamine level, which may induce changes at the receptor site and contribute to the appearance of "on-off" phenomena and dyskinesias. We compared a group of 18 patients treated for 60 consecutive months with continuous subcutaneous lisuride infusion with a group of 20 patients treated with conventional oral levodopa treatment. The clinical evaluations performed during the study showed in the lisuride group only a worsening of dyskinesias, whereas the other symptoms remained unchanged. In the other group the evaluation scores showed a significant worsening of all long-term treatment complications. The slow-release preparations of levodopa may ensure a more continuous dopaminergic stimulation than standard formulations. However, the use of these compounds is difficult in severely fluctuating patients because the lack of a plasma peak level usually leads to a very long delay before patients turn "on." We studied the pharmacokinetic and clinical effects of the two slow-release preparations of levodopa [Madopar HBS and Sinemet controlled-release (CR)] and a combination of Sinemet CR plus standard Sinemet in 13 fluctuating parkinsonian patients. The results of this study show that the combination of standard Sinemet and Sinemet CR ensures a more prolonged clinical effect with a very short latency to the "on" phase.
authors.affiliation: Department of Neurosciences, University La Sapienza, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Stocchi
authors.forename: P N
authors.initials: PN
authors.lastname: Patsalos
authors.forename: A
authors.initials: A
authors.lastname: Berardelli
authors.forename: L
authors.initials: L
authors.lastname: Barbato
authors.forename: A
authors.initials: A
authors.lastname: Bonamartini
authors.forename: M
authors.initials: M
authors.lastname: Manfredi
authors.forename: S
authors.initials: S
authors.lastname: Ruggieri
mesh_terms: D000368:Aged; D001545:Benserazide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D002230:Carbidopa / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D008090:Lisuride / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D010300:Parkinson Disease / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects
chemical_list: D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D001545:Benserazide; D008090:Lisuride; D002230:Carbidopa