Skip to main content

Advertisement

SpringerLink
Log in

Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation

  • Short communication
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Rotigotine, a non-ergolinic dopamine receptor agonist for treatment of Parkinson’s disease was continuously administered over 48 h (0.5 mg/kg s.c., slow release formulation) to conscious rats striatally implanted with a microdialysis probe. Subsequently, the levels of rotigotine increased to a maximum of 3.42 + 2.1 nmol/l and remained at a level of 2.81 ± 0.82 nmol/l for 48 h. Concomitantly, the dopamine levels consistently decreased to 20% of the control level. This suggests that the sustained administration of rotigotine provides stable extracellular drug levels in the striatum resulting in continuous stimulation of dopamine receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • CW Aretha A Sinha MP Galloway (1995) ArticleTitleDopamine D3-preferring ligands act at synthesis modulating autoreceptors J Pharmacol Exp Ther 274 609–613 Occurrence Handle1:CAS:528:DyaK2MXnsFSjsLg%3D Occurrence Handle7636720

    CAS  PubMed  Google Scholar 

  • F Bibbiani LC Costantini R Patel TN Chase (2005) ArticleTitleContinuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates Exp Neurol 192 73–78 10.1016/j.expneurol.2004.11.013 Occurrence Handle10.1016/j.expneurol.2004.11.013 Occurrence Handle1:CAS:528:DC%2BD2MXhtVKgsr8%3D Occurrence Handle15698620

    Article  CAS  PubMed  Google Scholar 

  • P de Boer P Enrico J Wright LD Wise W Timmerman E Moor et al. (1997) ArticleTitleCharacterization of the effect of dopamine D3 receptor stimulation on locomotion and striatal dopamine levels Brain Res 758 83–91 10.1016/S0006-8993(96)01438-2 Occurrence Handle10.1016/S0006-8993(96)01438-2 Occurrence Handle1:CAS:528:DyaK2sXjtlWgsbc%3D Occurrence Handle9203536

    Article  CAS  PubMed  Google Scholar 

  • EC de Lange MR Bouw JW Mandema M Danhof AG de Boer DD Breimer (1995) ArticleTitleApplication of intracerebral microdialysis to study regional distribution kinetics of drugs in rat brain Br J Pharmacol 116 2538–2544 Occurrence Handle1:CAS:528:DyaK2MXptlertLc%3D Occurrence Handle8581296

    CAS  PubMed  Google Scholar 

  • EC de Lange AG de Boer DD Breimer (2000) ArticleTitleMethodological issues in microdialysis sampling for pharmacokinetic studies Adv Drug Deliv Rev 45 125–148 10.1016/S0169-409X(00)00107-1 Occurrence Handle10.1016/S0169-409X(00)00107-1 Occurrence Handle1:CAS:528:DC%2BD3cXosFertbw%3D Occurrence Handle11108971

    Article  CAS  PubMed  Google Scholar 

  • WF Elmquist RJ Sawchuk (1997) ArticleTitleApplication of microdialysis in pharmacokinetic studies Pharm Res 14 267–288 10.1023/A:1012081501464 Occurrence Handle10.1023/A:1012081501464 Occurrence Handle1:CAS:528:DyaK2sXisVGlsrs%3D Occurrence Handle9098867

    Article  CAS  PubMed  Google Scholar 

  • WF Elmquist RJ Sawchuk (2000) ArticleTitleUse of microdialysis in drug delivery studies Adv Drug Deliv Rev 45 123–124 10.1016/S0169-409X(00)00105-8 Occurrence Handle10.1016/S0169-409X(00)00105-8 Occurrence Handle1:CAS:528:DC%2BD3cXosFertb8%3D Occurrence Handle11108970

    Article  CAS  PubMed  Google Scholar 

  • WM Guldenpfennig KH Poole KW Sommerville B Boroojerdi (2005) ArticleTitleSafety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease Clin Neuropharmacol 28 106–110 10.1097/01.wnf.0000162228.00154.ba Occurrence Handle10.1097/01.wnf.0000162228.00154.ba Occurrence Handle15965307

    Article  PubMed  Google Scholar 

  • M Hammarlund-Udenaes LK Paalzow EC de Lange (1997) ArticleTitleDrug equilibration across the blood–brain barrier — pharmacokinetic considerations based on the microdialysis method Pharm Res 14 128–134 10.1023/A:1012080106490 Occurrence Handle10.1023/A:1012080106490 Occurrence Handle1:CAS:528:DyaK2sXitFyrsbc%3D Occurrence Handle9090698

    Article  CAS  PubMed  Google Scholar 

  • P Jenner (2005) ArticleTitleA novel dopamine agonist for the transdermal treatment of Parkinson’s disease Neurology 65 S3–S5 10.1212/01.wnl.0000172666.23452.03 Occurrence Handle10.1212/01.wnl.0000172666.23452.03 Occurrence Handle1:CAS:528:DC%2BD2MXmtVSmsb0%3D Occurrence Handle16030291

    Article  CAS  PubMed  Google Scholar 

  • J Kehr (1999) Monitoring chemistry of brain microenvironment: biosensors, microdialysis and related techniques U Windhorst H Johansson (Eds) Modern techniques in neuroscience research Springer Berlin Heidelberg New York, Tokyo 1149–1198

    Google Scholar 

  • J Kehr X-J Hu T Yoshitake D Scheller (2006) ArticleTitleDetermination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection J Chromatography B Analyt Technol Biomed Life Sci 845 IssueID1 109–113 10.1016/j.jchromb.2006.07.066 Occurrence Handle10.1016/j.jchromb.2006.07.066

    Article  Google Scholar 

  • A Le Quellec S Dupin P Genissel S Saivin B Marchand G Houin (1995) ArticleTitleMicrodialysis probes calibration: gradient and tissue dependent changes in no net flux and reverse dialysis methods J Pharmacol Toxicol Methods 33 11–16 10.1016/1056-8719(94)00049-A Occurrence Handle10.1016/1056-8719(94)00049-A Occurrence Handle1:CAS:528:DyaK2MXjs1Whtrw%3D Occurrence Handle7727803

    Article  CAS  PubMed  Google Scholar 

  • P LeWitt (2005) ArticleTitleRotigotine: a viewpoint by Peter LeWitt CNS Drugs 19 983–984 10.2165/00023210-200519110-00008 Occurrence Handle10.2165/00023210-200519110-00008 Occurrence Handle16268668

    Article  PubMed  Google Scholar 

  • CM O’Hara A Uhland-Smith KL O’Malley RD Todd (1996) ArticleTitleInhibition of dopamine synthesis by dopamine D2 and D3 but not D4 receptors J Pharmacol Exp Ther 277 186–192 Occurrence Handle8613917

    PubMed  Google Scholar 

  • InstitutionalAuthorNameParkinson Study Group (2003) ArticleTitleA controlled trial of rotigotine monotherapy in early Parkinson’s disease Arch Neurol 60 1721–1728 10.1001/archneur.60.12.1721 Occurrence Handle10.1001/archneur.60.12.1721

    Article  Google Scholar 

  • W Poewe F Luessi (2005) ArticleTitleClinical studies with transdermal rotigotine in early Parkinson’s disease Neurology 65 S11–S14 Occurrence Handle1:STN:280:DC%2BD2MznsValsQ%3D%3D Occurrence Handle16030290

    CAS  PubMed  Google Scholar 

  • NA Reynolds K Wellington SE Easthope (2005) ArticleTitleRotigotine: in Parkinson’s disease CNS Drugs 19 973–981 10.2165/00023210-200519110-00006 Occurrence Handle10.2165/00023210-200519110-00006 Occurrence Handle1:CAS:528:DC%2BD2MXhtlSjsbrK Occurrence Handle16268667

    Article  CAS  PubMed  Google Scholar 

  • RH Roth MC Nowycky (1977) ArticleTitleNonstriatal dopaminergic neurons: role of presynaptic receptors in the modulation of transmitter synthesis Adv Biochem Psychopharmacol 16 465–470 Occurrence Handle1:CAS:528:DyaE2sXlt1Onu7k%3D Occurrence Handle18895

    CAS  PubMed  Google Scholar 

  • DKA Scheller (2006) ArticleTitleExtended receptor profile of rotigotine, a non-ergolinic dopamine agonist being investigated in Parkinson’s disease Mov Disord 21 S80

    Google Scholar 

  • D Scheller J Kolb (1991) ArticleTitleThe internal reference technique in microdialysis: a practical approach to monitoring dialysis efficiency and to calculating tissue concentration from dialysate samples J Neurosci Methods 40 31–38 10.1016/0165-0270(91)90114-F Occurrence Handle10.1016/0165-0270(91)90114-F Occurrence Handle1:CAS:528:DyaK38Xks1Gqs70%3D Occurrence Handle1795551

    Article  CAS  PubMed  Google Scholar 

  • W Timmerman BH Westerink JB De Vries PG Tepper AS Horn (1989) ArticleTitleMicrodialysis and striatal dopamine release: stereoselective actions of the enantiomers of N-0437 Eur J Pharmacol 162 143–150 10.1016/0014-2999(89)90614-6 Occurrence Handle10.1016/0014-2999(89)90614-6 Occurrence Handle1:CAS:528:DyaL1MXitVGnu7s%3D Occurrence Handle2566492

    Article  CAS  PubMed  Google Scholar 

  • U Ungerstedt (1991) ArticleTitleMicrodialysis — principles and applications for studies in animals and man J Intern Med 230 365–373 Occurrence Handle10.1111/j.1365-2796.1991.tb00459.x Occurrence Handle1:STN:280:DyaK38%2FhtlOluw%3D%3D Occurrence Handle1919432

    Article  CAS  PubMed  Google Scholar 

  • X Wang PN Patsalos (2003) ArticleTitleA comparison of central brain (cerebrospinal and extracellular fluids) and peripheral blood kinetics of phenytoin after intravenous phenytoin and fosphenytoin Seizure 12 330–336 10.1016/S1059-1311(03)00099-2 Occurrence Handle10.1016/S1059-1311(03)00099-2 Occurrence Handle1:CAS:528:DC%2BD3sXjsVelu7o%3D Occurrence Handle12915078

    Article  CAS  PubMed  Google Scholar 

  • TC Westfall MJ Besson MF Giorguieff J Glowinski (1976) ArticleTitleThe role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum Naunyn Schmiedebergs Arch Pharmacol 292 279–287 10.1007/BF00517390 Occurrence Handle10.1007/BF00517390 Occurrence Handle1:CAS:528:DyaE28Xhs1amsbY%3D Occurrence Handle181686

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    J. Kehr & M. Goiny

  2. Pronexus Analytical AB, Karolinska Science Park, Stockholm, Sweden

    J. Kehr & X.-J. Hu

  3. Department of Pharmacology/Toxicology, Schwarz Biosciences, Monheim, Germany

    D. K. A. Scheller

Authors
  1. J. Kehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X.-J. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Goiny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. K. A. Scheller
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kehr, J., Hu, XJ., Goiny, M. et al. Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation. J Neural Transm 114, 1027–1031 (2007). https://doi.org/10.1007/s00702-007-0719-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-007-0719-3

Search

Navigation