You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.


ABOUT ARCHIVES
Advanced Search

Welcome   | My Account | E-mail Alerts | Access Rights | Sign In


  Vol. 49 No. 11, November 1992 TABLE OF CONTENTS
  Archives
  •  Online Features
  ORIGINAL CONTRIBUTIONS
 This Article
 •References
 •Full text PDF
 • Reply to article
 •Send to a friend
 • Save in My Folder
 •Save to citation manager
 •Permissions
 Citing Articles
 •Citation map
 •Citing articles on HighWire
 •Contact me when this article is cited
 Related Content
 •Similar articles in this journal
 Social Bookmarking
  Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit Add to Technorati Add to Twitter What's this?

Effect of Long-term Therapy on the Pharmacodynamics of Levodopa

Relation to On-Off Phenomenon

John G. Nutt, MD; William R. Woodward, PhD; Julie H. Carter, RN, MN; Stephen T. Gancher, MD

Arch Neurol. 1992;49(11):1123-1130.


Abstract

• To determine how the response to levodopa is altered by long-term therapy, we examined the dose response to 2-hour infusions of levodopa in three groups of parkinsonian patients: those who were previously untreated, those who exhibited stable responses, and those who exhibited fluctuating responses to levodopa therapy, using tapping speed as an index of bradykinesia. The baseline tapping speed was greater in the patients with stable responses than in the untreated patients, probably representing a "long-duration response" to levodopa therapy. A "short-duration response," indicated by an increase in tapping speed lasting hours, was observed in most patients in all groups. The onset of the short-duration effect was more rapid and the incremental increase in tapping speed was twice as large in the patients with fluctuating responses compared with the untreated patients and patients with stable responses. The duration of the short-duration effect was greatest in the untreated group but did not differ between the groups with stable and fluctuating responses. Dyskinesia was not observed in any of the de novo patients but was observed in three of 12 patients with stable responses and eight of nine patients with fluctuating responses to levodopa therapy. Dyskinesia appeared before or with the antiparkinsonian effects in patients with stable responses, giving no indication of a higher threshold for dyskinesia in these patients compared with those with fluctuating responses. The plasma half-life clearance, volume of distribution, and maximum plasma concentrations of levodopa did not differ among groups. We conclude that (1) part of what has been considered an extended short-duration response to levodopa therapy in patients with stable responses represents instead the long-duration response; (2) a short-duration response, albeit subtle, is present in most patients from the initiation of levodopa therapy; and (3) an increase in the magnitude of the short-duration response and the appearance of dyskinesia cause the fluctuations to become clinically important, whereas a shortening of the duration of the response is not critical.



Author Affiliations

From the Departments of Neurology (Drs Nutt, Woodward, and Gancher and Ms Carter), Pharmacology (Dr Nutt), and Biochemistry and Molecular Biology (Dr Woodward), School of Medicine, and the Department of Adult Health and Illness, School of Nursing (Ms Carter), Oregon Health Sciences University, Portland.


Footnotes

Accepted for publication May 12, 1992.

Reprint requests to Oregon Health Science University, 3181 Sam Jackson Park Rd SW, L226, Portland, OR 97201-3098 (Dr Nutt).



Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Dopamine Gene Therapy for Parkinson's Disease in a Nonhuman Primate Without Associated Dyskinesia
Jarraya et al.
Sci Transl Med 2009;1:2ra4-2ra4.
ABSTRACT | FULL TEXT  

Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia
Lee et al.
Brain 2008;131:1574-1587.
ABSTRACT | FULL TEXT  

Evaluation of Levodopa Dose and Magnitude of Dopamine Depletion as Risk Factors for Levodopa-Induced Dyskinesia in a Rat Model of Parkinson's Disease
Putterman et al.
J. Pharmacol. Exp. Ther. 2007;323:277-284.
ABSTRACT | FULL TEXT  

Patterns of levodopa response in Parkinson's disease: a clinico-pathological study
Kempster et al.
Brain 2007;130:2123-2128.
ABSTRACT | FULL TEXT  

Levodopa-induced dyskinesia in Parkinson's disease: clinical features, pathogenesis, prevention and treatment
Thanvi et al.
Postgrad. Med. J. 2007;83:384-388.
ABSTRACT | FULL TEXT  

Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study.
Pavese et al.
Neurology 2006;67:1612-1617.
ABSTRACT | FULL TEXT  

The origin of motor fluctuations in Parkinson's disease: Importance of dopaminergic innervation and basal ganglia circuits
Obeso et al.
Neurology 2004;62:S17-30.
ABSTRACT | FULL TEXT  

The MPTP-treated primate as a model of motor complications in PD: Primate model of motor complications
Jenner
Neurology 2003;61:S4-11.
ABSTRACT | FULL TEXT  

Response to levodopa in parkinsonian patients with bilateral subthalamic nucleus stimulation
Moro et al.
Brain 2002;125:2408-2417.
ABSTRACT | FULL TEXT  

Relevance of motor complications in Parkinson's disease
Adler
Neurology 2002;58:S51-56.
ABSTRACT | FULL TEXT  

Response to Levodopa Treatment in Dopa-Responsive Dystonia
Nutt and Nygaard
Arch Neurol 2001;58:905-910.
ABSTRACT | FULL TEXT  

The long-duration response to L-dopa in the treatment of early PD
Zappia et al.
Neurology 2000;54:1910-1915.
ABSTRACT | FULL TEXT  

Vesicular Monoamine Transporter-2 and Aromatic L-Amino Acid Decarboxylase Enhance Dopamine Delivery after L-3,4-Dihydroxyphenylalanine Administration in Parkinsonian Rats
Lee et al.
J. Neurosci. 1999;19:3266-3274.
ABSTRACT | FULL TEXT  

Loss of long-duration response to levodopa over time in PD: Implications for wearing-off
Zappia et al.
Neurology 1999;52:763-763.
ABSTRACT | FULL TEXT  





HOME | CURRENT ISSUE | PAST ISSUES | TOPIC COLLECTIONS | CME | SUBMIT | SUBSCRIBE | HELP
CONDITIONS OF USE | PRIVACY POLICY | CONTACT US | SITE MAP
 
© 1992 American Medical Association. All Rights Reserved.