The response to levodopa in Parkinson's disease: Imposing pharmacological law and order

John G. Nutt, Nicholas H.G. Holford

Research output: Contribution to journalReview article

277 Scopus citations

Abstract

The seemingly unpredictable response to levodopa in patients with Parkinson's disease can be understood as an interaction between several distinct pharmacological effects of levodopa. The most important are a short- duration response with a half-life of minutes to hours and a long-duration response with a half-life of days, superimposed on diurnal motor variation. A negative response characterized by brief worsening before and after the short-duration response and dyskinesia accentuate the short-duration response. These various responses are modified by disease progression and long-term levodopa therapy. Pharmacodynamic modeling of the short-duration response indicates that with time, the response becomes less graded and small changes in levodopa concentrations can produce big changes in response. In this setting, unpredictability arises from the variation in absorption and distribution of levodopa.

Original languageEnglish (US)
Pages (from-to)561-573
Number of pages13
JournalAnnals of Neurology
Volume39
Issue number5
DOIs
StatePublished - May 1996

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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