Movement Disorders, Parkinson's Disease
Read Time: 2 mins

Subcutaneous Apomorphine Infusion – An Update

Copy Link
Published Online: Jul 15th 2012 European Neurological Review, 2012;7(Suppl. 1):8–12 DOI:
Authors: Regina Katzenschlager
Quick Links:
Article Information

Continuous delivery of dopaminergic drugs is an important treatment strategy to delay or reverse motor complications in Parkinson’s disease (PD). Subcutaneous apomorphine (APO) infusion has been shown (in uncontrolled studies) to significantly reduce ‘off’ time and dyskinesia duration and severity, and long-term data show the beneficial effects persist for several years. There is some evidence that the maximum antidyskinetic effect of APO infusion may be attained when oral medications are reduced or discontinued, making monotherapy an important clinical goal. Recent studies demonstrate possible positive effects of APO infusion on the non-motor symptoms of PD. However, more trials are needed to assess the neuropsychiatric effects of this treatment. Moreover, randomised controlled trials are needed to compare APO infusion with best medical treatment and with other invasive treatments such as levodopa/carbidopa intestinal gel infusion and deep brain stimulation.


Parkinson’s disease, levodopa, continuous dopaminergic stimulation, subcutaneous apomorphine, non-motor symptoms


The management of the later stages of Parkinson’s disease (PD) is greatly impacted by non-dopaminergic problems, such as dementia, depression and falls, and by the emergence of motor complications including motor fluctuations and dyskinesias. Motor fluctuations, such as ‘wearing off’ and unpredictable ‘off’, affect 30–100 % of patients.1–4 Dyskinesias can be ‘on’ (mostly choreatic), biphasic (often dystonic) or ‘off’ (dystonic). In the later stages of the disease, there is a loss of nigrostriatal neurons and a concomitant loss of storage capacity. Positron emission tomography imaging of dyskinetic and non-dyskinetic patients showed no difference in dopamine receptor binding, which suggests that dyskinesias are unlikely to be the effect of alterations in striatal dopamine receptor binding.5 On the other hand, levodopa-induced changes in synaptic dopamine levels increase with the progression of PD.6 These changes in synaptic dopamine concentration may be a factor in the emergence of peak-dose dyskinesias.

The pharmacokinetics of levodopa in the periphery, such as plasma half-life clearance, volume of distribution and maximum plasma concentrations, remain unchanged.7 However, the absorption f oral levodopa, which takes place primarily in the duodenum, is affected as gastric emptying becomes more erratic.8,9 Pharmacodynamic postsynaptic striatal changes in gene expression,10 neuropeptide formation11 and discharge patterns of the basal ganglia12 result in complex feedback loops.13 Furthermore, non-dopaminergic factors such as glutamate, opioids and serotoninmay be involved in the development of dyskinesia.14 Sprouting of extrasynaptic dopaminergic terminals may also lead to dysregulateddopamine release.15

One of the most important factors associated with the risk of motor complications is the degree of neuronal loss. In rats whose nigrostriatal system had been lesioned unilaterally by 6-hydroxydopamine, the level of levodopa-induced motor complications was related to lesion size.16 In humans, if the first dose of levodopa is given at an advanced stage of the disease, motor complications may develop within a matter of weeks.17 Furthermore, patients with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced chronic and severe parkinsonism developed dyskinesias or ‘on-off’ fluctuations within months of starting levodopa treatment.14 Additional factors that contribute to a greater risk of motor complications include younger age at disease onset,3,18 lower bodyweight19,20 and genetic factors.21

To view the full article in PDF or eBook formats, please click on the icons above.

Article Information:

Regina Katzenschlager has received consulting and lecturing fees from Abbott, Cephalon, Lundbeck, Teva, Boehringer, GlaxoSmithKline, Novartis and Genus.


Regina Katzenschlager, Department of Neurology, Danube Hospital, Langobardenstr. 122, 1220 Vienna, Austria. E:


The V International Forum on Parkinson’s Disease (Helsinki, Finland, 6–7 May 2011) was funded by an unrestricted educational grant from Abbott. Abbott funded the development of this supplement by ESP Bioscience (Crowthorne, UK). Emily Chu and Nicole Meinel of ESP Bioscience provided medical writing and editorial support to the author in the development of this publication. Abbott had the opportunity to review and comment on the publication’s content; however, all decisions regarding content were made by the author.




  1. Ahlskog JE, Muenter MD, Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature, Mov Disord, 2001;16:448–58.
  2. Stacy M, Bowron A, Guttman M, et al., Identification of motor and nonmotor wearing-off in Parkinson’s disease: comparison of a patient questionnaire versus a clinician assessment, Mov Disord, 2005;20:726–33.
  3. Schrag A, Quinn N, Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study, Brain, 2000;123:2297–305.
  4. Parkinson Study Group, Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa, Ann Neurol, 1996;39:37–45.
  5. Turjanski N, Lees AJ, Brooks DJ, In vivo studies on striatal dopamine D1 and D2 site binding in L-dopa-treated Parkinson’s disease patients with and without dyskinesias, Neurology, 1997;49:717–23.
  6. de la Fuente-Fernández R, Sossi V, Huang Z, et al., Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias, Brain, 2004;127:2747–54.
  7. Nutt JG, Woodward WR, Carter JH, Gancher ST, Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on-off phenomenon, Arch Neurol, 1992;49:1123–30.
  8. Stocchi F, The hypothesis of the genesis of motor complications and continuous dopaminergic stimulation in the treatment of Parkinson’s disease, Parkinsonism Relat Disord, 2009;15(Suppl. 1):S9–S15.
  9. Nutt JG, Fellman JH, Pharmacokinetics of levodopa, Clin Neuropharmacol, 1984;7:35–49.
  10. Gerfen CR, Engber TM, Mahan LC, et al., D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons, Science, 1990;250:1429–32.
  11. Morissette M, Goulet M, Soghomonian JJ, et al., Preproenkephalin mRNA expression in the caudateputamen of MPTP monkeys after chronic treatment with the D2 agonist U91356A in continuous or intermittent mode of administration: comparison with L-DOPA therapy, Brain Res Mol Brain Res, 1997;49:55–62.
  12. Obeso JA, Rodríguez-Oroz MC, Benitez-Temino B, et al., Functional organization of the basal ganglia: therapeutic implications for Parkinson’s disease, Mov Disord, 2008;23(Suppl. 3):S548–59.
  13. Jenner P, Molecular mechanisms of L-DOPA-induced dyskinesia, Nat Rev Neurosci, 2008;9:665–77.
  14. Carta M, Carlsson T, Kirik D, Björklund A, Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats, Brain, 2007;130:1819–33.
  15. Lee J, Zhu WM, Stanic D, et al., Sprouting of dopamine terminals and altered dopamine release and uptake in Parkinsonian dyskinaesia, Brain, 2008;131:1574–87.
  16. Papa SM, Engber TM, Kask AM, Chase TN, Motor fluctuations in levodopa treated parkinsonian rats: relation to lesion extent and treatment duration, Brain Res, 1994;662:69–74.
  17. Onofrj M, Paci C, Thomas A, Sudden appearance of invalidating dyskinesia-dystonia and off fluctuations after the introduction of levodopa in two dopaminomimetic drug naive patients with stage IV Parkinson’s disease, J Neurol Neurosurg Psychiatry, 1998;65:605–6.
  18. Kumar N, Van Gerpen JA, Bower JH, Ahlskog JE, Levodopadyskinesia incidence by age of Parkinson’s disease onset, Mov Disord, 2005;20:342–4.
  19. Arabia G, Zappia M, Bosco D, et al., Body weight, levodopa pharmacokinetics and dyskinesia in Parkinson’s disease, Neurol Sci, 2002;23(Suppl. 2):S53–4.
  20. Sharma JC, Macnamara L, Hasoon M, et al., Cascade of levodopa dose and weight-related dyskinesia in Parkinson’s disease (LD-WD-PD cascade), Parkinsonism Relat Disord, 2006;12:499–505.
  21. Foltynie T, Cheeran B, Williams-Gray CH, et al., BDNF val66met influences time to onset of levodopa induced dyskinesia in Parkinson’s disease, J Neurol Neurosurg Psychiatry, 2009;80:141–4.
  22. Grandas F, Galiano ML, Tabernero C, Risk factors for levodopa-induced dyskinesias in Parkinson’s disease, J Neurol, 1999;246:1127–33.
  23. Olanow CW, Obeso JA, Stocchi F, Continuous dopaminereceptor treatment of Parkinson’s disease: scientific rationale and clinical implications, Lancet Neurol, 2006;5:677–87.
  24. Rascol O, Brooks DJ, Korczyn AD, et al., 056 Study Group, A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa, N Engl J Med, 2000;342:1484–91.
  25. Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y, Ten-year follow-up of three different initial treatments in de-novo PD: a randomized trial, Neurology, 2001;57:1687–94.
  26. Bracco F, Battaglia A, Chouza C, et al., The long-acting dopamine receptor agonist cabergoline in early Parkinson’s disease: final results of a 5-year, double-blind, levodopacontrolled study, CNS Drugs, 2004;18:733–46.
  27. Katzenschlager R, Head J, Schrag A, et al., Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD, Neurology, 2008;71:474–80.
  28. Nilsson D, Nyholm D, Aquilonius SM, Duodenal levodopa infusion in Parkinson’s disease – long-term experience, Acta Neurol Scand, 2001;104:343–8.
  29. Nyholm D, Askmark H, Gomes-Trolin C, et al., Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets, Clin Neuropharmacol, 2003;26:156–63.
  30. Syed N, Murphy J, Zimmerman T, Jr., et al., Ten years’ experience with enteral levodopa infusions for motor fluctuations in Parkinson’s disease, Mov Disord, 1998;13:336–8.
  31. Colzi A, Turner K, Lees AJ, Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson’s disease, J Neurol Neurosurg Psychiatry, 1998;64:573–6.
  32. Manson AJ, Turner K, Lees AJ, Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson’s disease: long-term follow-up study of 64 patients, Mov Disord, 2002;17:1235–41.
  33. Katzenschlager R, Hughes A, Evans A, et al., Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson’s disease: a prospective study using single-dose challenges, Mov Disord, 2005;20:151–7.
  34. Dewey RB Jr, Maraganore DM, Ahlskog JE, Matsumoto JY, Intranasal apomorphine rescue therapy for parkinsonian ‘off’ periods, Clin Neuropharmacol, 1996;19:193–201.
  35. Dewey RB Jr, Hutton JT, LeWitt PA, Factor SA, A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events, Arch Neurol, 2001;58:1385–92.
  36. Frankel JP, Lees AJ, Kempster PA, Stern GM, Subcutaneous apomorphine in the treatment of Parkinson’s disease, J Neurol Neurosurg Psychiatry, 1990;53:96–101.
  37. Hughes AJ, Bishop S, Kleedorfer B, et al., Subcutaneous apomorphine in Parkinson’s disease: response to chronic administration for up to five years, Mov Disord, 1993;8:165–70.
  38. Wenning GK, Bösch S, Luginger E, et al., Effects of longterm, continuous subcutaneous apomorphine infusions on motor complications in advanced Parkinson’s disease, Adv Neurol, 1999;80:545–8.
  39. Poewe W, Kleedorfer B, Wagner M, et al., Continuous subcutaneous apomorphine infusions for fluctuating Parkinson’s disease. Long-term follow-up in 18 patients, Adv Neurol, 1993;60:656–9.
  40. Kanovsky P, Kubová D, Bares M, et al., Levodopa-induced dyskinesias and continuous subcutaneous infusions of apomorphine: results of a two-year, prospective follow-up, Mov Disord, 2002;17:188–91.
  41. Stocchi F, Vacca L, De Pandis MF, et al., Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson’s disease: long-term results, Neurol Sci, 2001;22:93–4.
  42. Antonini A, Isaias IU, Rodolfi G, et al., A 5-year prospective assessment of advanced Parkinson disease patients treated with subcutaneous apomorphine infusion or deep brain stimulation, J Neurol, 2011;258:579–85.
  43. García Ruiz PJ, Sesar Ignacio A, Ares Pensado B, et al., Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson’s disease with motor fluctuations: a multicenter study, Mov Disord, 2008;23:1130–6.
  44. Sixel-Döring F, Klinke H, Hahn K, et al., [Subcutaneous apomorphine infusion therapy in advanced Parkinson’s disease: Long-term follow-up of effectivity, tolerability and patient satisfaction], Akt Neurol, 2011;38:S27–S33.
  45. Manson AJ, Hanagasi H, Turner K, et al., Intravenous apomorphine therapy in Parkinson’s disease: clinical and pharmacokinetic observations, Brain, 2001;124:331–40.
  46. Martinez-Martin P, Reddy P, Antonini A, et al., Chronic subcutaneous infusion therapy with apomorphine in advanced Parkinson’s disease compared to conventional therapy: a real life study of non motor effect, J Parkinsons Dis, 2011;1:197–203.
  47. Alegret M, Valldeoriola F, Martí M, et al., Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson’s disease, Mov Disord, 2004;19:1463–9.
  48. De Gaspari D, Siri C, Landi A, et al., Clinical and neuropsychological follow up at 12 months in patients with complicated Parkinson’s disease treated with subcutaneous apomorphine infusion or deep brain stimulation of the subthalamic nucleus, J Neurol Neurosurg Psychiatry, 2006;77:450–3.
  49. Morgante L, Basile G, Epifanio A, et al., Continuous apomorphine infusion (CAI) and neuropsychiatric disorders in patients with advanced Parkinson’s disease: a follow-up of two years, Arch Gerontol Geriatr Suppl, 2004:291–6.
  50. Di Rosa AE, Epifanio A, Antonini A, et al., Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson’s disease, Neurol Sci, 2003;24:174–5.
  51. Deleu D, Hanssens Y, Northway MG, Subcutaneous apomorphine : an evidence-based review of its use in Parkinson’s disease, Drugs Aging, 2004;21:687–709.
  52. Kehr J, Hu XJ, Goiny M, Scheller DK, Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation, J Neural Transm, 2007;114:1027–31.
  53. Hely MA, Reid WG, Adena MA, et al., The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years, Mov Disord, 2008;23:837–44.

Further Resources

Share this Article
Related Content In Parkinson's Disease
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72