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

John Nutt, Nicholas H G Holford

Research output: Contribution to journalArticle

272 Citations (Scopus)

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

Fingerprint

Levodopa
Parkinson Disease
Pharmacology
Half-Life
Dyskinesias
Disease Progression

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The response to levodopa in Parkinson's disease : Imposing pharmacological law and order. / Nutt, John; Holford, Nicholas H G.

In: Annals of Neurology, Vol. 39, No. 5, 05.1996, p. 561-573.

Research output: Contribution to journalArticle

@article{1cdc24d1d2df4b23b8fdfd1e96081894,
title = "The response to levodopa in Parkinson's disease: Imposing pharmacological law and order",
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.",
author = "John Nutt and Holford, {Nicholas H G}",
year = "1996",
month = "5",
doi = "10.1002/ana.410390504",
language = "English (US)",
volume = "39",
pages = "561--573",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - The response to levodopa in Parkinson's disease

T2 - Imposing pharmacological law and order

AU - Nutt, John

AU - Holford, Nicholas H G

PY - 1996/5

Y1 - 1996/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029883235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029883235&partnerID=8YFLogxK

U2 - 10.1002/ana.410390504

DO - 10.1002/ana.410390504

M3 - Article

C2 - 8619540

AN - SCOPUS:0029883235

VL - 39

SP - 561

EP - 573

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -