Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study | Movement Disorders | JAMA Neurology | JAMA Network
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1.
Kuoppamäki  MAl-Barghouthy  GJackson  M  et al.  Beginning-of-dose and rebound worsening in MPTP-treated common marmosets treated with levodopa.  Mov Disord 2002;17 (6) 1312- 1317PubMedGoogle ScholarCrossref
2.
Contin  MRiva  RMartinelli  P  et al.  Kinetic-dynamic relationship of oral levodopa: possible biphasic response after sequential doses in Parkinson's disease.  Mov Disord 1992;7 (3) 244- 248PubMedGoogle ScholarCrossref
3.
Merello  MLees  AJ Beginning-of-dose motor deterioration following the acute administration of levodopa and apomorphine in Parkinson's disease.  J Neurol Neurosurg Psychiatry 1992;55 (11) 1024- 1026PubMedGoogle ScholarCrossref
4.
Nutt  JGGancher  STWoodward  WR Does an inhibitory action of levodopa contribute to motor fluctuations?  Neurology 1988;38 (10) 1553- 1557PubMedGoogle ScholarCrossref
5.
Paalzow  GHMPaalzow  LK L-Dopa: how it may exacerbate parkinsonian symptoms.  Trends Pharmacol Sci 1986;715- 19Google ScholarCrossref
6.
Benoit-Marand  MBorrelli  EGonon  F Inhibition of dopamine release via presynaptic D2 receptors: time course and functional characteristics in vivo.  J Neurosci 2001;21 (23) 9134- 9141PubMedGoogle Scholar
7.
Hjorth  SCarlsson  AWilkstrom  H  et al.  3-PPP, a new centrally acting DA-receptor agonist with selectivity for autoreceptors.  Life Sci 1981;28 (11) 1225- 1238PubMedGoogle ScholarCrossref
8.
Di Chiara  GPorceddu  MLFratta  WGessa  GL Postsynaptic receptors are not essential for dopaminergic feedback regulation.  Nature 1977;267 (5608) 270- 272PubMedGoogle ScholarCrossref
9.
Richard  MGBennett  J Regulation by D2 dopamine receptors of in vivo dopamine synthesis in striata of rats and mice with experimental parkinsonism.  Exp Neurol 1994;129 (1) 57- 63PubMedGoogle ScholarCrossref
10.
Yarkov  AVHanger  DReploge  MJoyce  J Behavioral effects of dopamine agonists and antagonists in MPTP-lesioned D3 receptor knockout mice.  Pharmacol Biochem Behav 2003;76 (3-4) 551- 562PubMedGoogle ScholarCrossref
11.
Ingram  WMPriston  MJSewell  GJ Improved assay for R(-)-apomorphine with application to clinical pharmacokinetic studies in Parkinson's disease.  J Chromatogr B Analyt Technol Biomed Life Sci 2006;831 (1-2) 1- 7PubMedGoogle ScholarCrossref
12.
Gancher  STWoodward  WRNutt  JG Apomorphine tolerance in Parkinson's disease: lack of a dose effect.  Clin Neuropharmacol 1996;19 (1) 59- 64PubMedGoogle ScholarCrossref
13.
Nutt  JGWoodward  WRHammerstad  JPCarter  JHAnderson  JL The “on-off” phenomenon in Parkinson's Disease.  N Engl J Med 1984;310 (8) 483- 488PubMedGoogle ScholarCrossref
14.
Minguez-Castellanos  AEscamilla-Sevilla  FKatati  M  et al.  Different patterns of medication change after subthalamic or pallidal stimulation for Parkinson's disease: target related effect or selection bias?  J Neurol Neurosurg Psychiatry 2005;76 (1) 34- 39PubMedGoogle ScholarCrossref
15.
Harder  SBaas  H Concentration-response relationship of levodopa in patients at different stages of Parkinson's disease.  Clin Pharmacol Ther 1998;64 (2) 183- 191PubMedGoogle ScholarCrossref
16.
Kellett  MWSteiger  MJ Deterioration in parkinsonism with low-dose pergolide.  J Neurol 1999;246 (4) 309- 311PubMedGoogle ScholarCrossref
17.
Grosset  KGrosset  DLees  A Trial of subtherapeutic pergolide in de novo Parkinson's disease.  Mov Disord 2005;20 (3) 363- 366PubMedGoogle ScholarCrossref
18.
Baas  HHarder  SBurklin  FDemisch  LFischer  PA Pharmacodynamics of levodopa coadministered with apomorphine in parkinsonian patients with end-of-dose motor fluctuations.  Clin Neuropharmacol 1998;21 (2) 86- 92PubMedGoogle Scholar
19.
Ekesbo  ARydin  ETorstenson  RSydow  OLaengstrom  BTedroff  J Dopamine autoreceptor function is lost in advanced Parkinson's disease.  Neurology 1999;52 (1) 120- 125PubMedGoogle ScholarCrossref
20.
de la Fuente-Fernández  RLim  ASSossi  V  et al.  Apomorphine-induced changes in synaptic dopamine levels: positron emission tomography evidence for presynaptic inhibition.  J Cereb Blood Flow Metab 2001;21 (10) 1151- 1159PubMedGoogle ScholarCrossref
21.
Volkow  NDSwanson  JM Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD.  Am J Psychiatry 2003;160 (11) 1909- 1918PubMedGoogle ScholarCrossref
Clinical Trials
February 2008

Effect of Low Concentrations of Apomorphine on Parkinsonism in a Randomized, Placebo-Controlled, Crossover Study

Author Affiliations

Author Affiliations:Parkinson's Disease Research, Education, and Clinical Center, Portland VA Medical Center, Portland, Oregon (Drs Gunzler and Nutt); and Parkinson Center of Oregon (Drs Gunzler and Nutt), Oregon Clinical and Translational Research Institute (Ms Koudelka), Division of Biostatistics, Department of Public Health & Preventive Medicine (Dr Carlson), and Department of Biomedical Engineering (Dr Pavel), Oregon Health & Sciences University, Portland. Dr Gunzler is now with the Movement Disorders Center, University Hospitals Case Medical Center and Case Western Reserve University School of Medicine, Cleveland, Ohio.

 

IRASHOULSONMD

Arch Neurol. 2008;65(2):193-198. doi:10.1001/archneurol.2007.58
Abstract

Objective  To determine whether low concentrations of a dopamine agonist worsen parkinsonism, which would suggest that activation of presynaptic dopamine autoreceptors causes a super-off state.

Design  Randomized, double-blind, placebo-controlled, crossover clinical trial.

Setting  Academic movement disorders center.

Patients  Patients with Parkinson disease and motor fluctuations.

Intervention  Fourteen patients with Parkinson disease and motor fluctuations were randomized to receive 1 of 6 possible sequences of placebo, low-dose (subthreshold) apomorphine hydrochloride, and high-dose (threshold to suprathreshold) apomorphine hydrochloride infusions. Subthreshold doses of apomorphine hydrochloride (12.5 μg/kg/h every 2 hours and 25 μg/kg/h every 2 hours), threshold to suprathreshold doses of apomorphine hydrochloride (50 μg/kg/h every 2 hours and 100 μg/kg/h every 2 hours), and placebo were infused for 4 hours daily for 3 consecutive days.

Main Outcome Measures  Finger and foot tapping rates.

Results  There was no decline in finger or foot tapping rates during the low-dose apomorphine hydrochloride infusions relative to placebo. The high-dose infusions increased foot tapping (P < .001) and trended toward increasing finger tapping compared with placebo infusions.

Conclusions  Subthreshold concentrations of apomorphine did not worsen parkinsonism, suggesting that presynaptic dopamine autoreceptors are not important to the motor response in moderate to advanced Parkinson disease.

Trial Registration  clinicaltrials.gov Identifier: NCT00472355

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