EBM Consult

If Patients with Parkinson's Disease are Deficient in Dopamine, Why Then is Peripheral Dopamine Administration Not Effective at Treating the Bradykinesia, Rigidity, and Resting Tremor?


  • Patients with Parkinson's disease are known to have a depletion of dopaminergic neurons in the substantia nigra in the brain which results in problems with both initiation and coordination of muscle movement.
  • As such, increasing the amount of dopamine in the brain can improve symptoms.  Unfortunately, peripherally administered dopamine cannot penetrate the blood brain barrier and thus is ineffective.
  • The precursor of dopamine is levodopa.  It can penetrate the blood brain barrier where it is then converted to dopamine by amino acid decarboxylase or dopa decarboxylase enzyme.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Donald S. Nuzum, PharmD, BCACP, CDE
Last Reviewed:
August 2015


  • According to the Parkinson's Disease Foundation, there are approximately one million individuals in the United States alone who live with Parkinson's disease with about 50,000 individuals being diagnosed each year with no preference in gender.1,2  While Parkinson's disease is generally considered a disease that increases with age or primarily affects the elderly, approximately 4% of patients under the age of 50 will be diagnosed with the disease.1    

    As it relates to the basic pathophysiology of Parkinson's disease, patients are known to have a deficiency of dopamine producing neurons in the brain.2  In particular, the dopaminergic neurons within the substantia nigra begin to degenerate where they eventually will no longer send dopamine to the corpus striatum.  This decrease in dopamine production and release in the striatum leads to an overall net inhibition of the thalamus and communication to the cerebral cortex for proper modulation of motor movements (mainly initiation and coordination of muscle movement).  As such, patients with Parkinson's disease will commonly experience or exhibit bradykinesia (slow voluntary motor movement), rigidity (increased resistance to passive movements) and resting tremor.2,3  In order to correct or minimize these complications, patients will need drug therapy that can increase the amount of dopamine available to influence the basal ganglia. The most common approach to the management of Parkinson's disease is to increase the production or availability of dopamine in the brain. One of the most common medications used is the precursor to dopamine, levodopa (L-Dopa; 3,4-dihydroxyphenyl-L-alanine).  It is generally given in combination with carbidopa to improve the efficacy and reduce the side effects.4 

    Why doesn't peripheral dopamine administration work in the management of Parkinson's disease if that is what these patients are in need of most?

    Peripherally administered (outside of the central nervous system) dopamine is not effective because it cannot cross the blood brain barrier.4  The reason for its inability to cross the blood brain barrier has to do with at least two influencing factors.  The first is that dopamine is a hydrophilic molecule that has a greater degree of difficulty in crossing cell membranes.  The second is the absence of a transporter for dopamine to get past the blood brain barrier and into the brain.6  Since the increase in dopamine concentrations are needed in the brain and the peripheral administration of dopamine cannot get into the brain, it does not work in the management of symptoms seen in Parkinson's disease.  However, the precursor to dopamine, L-dopa, is able to get into the brain via a sodium-independent transport system called, large neutral amino acid carrier system or L (leucine) system.7  Once L-dopa gets inside the brain it can then be metabolized by dopa decarboxylase or amino acid decarboxylase to form dopamine within the dopaminergic neurons within the substantia nigra.4  Therefore, L-dopa versus peripherally administered dopamine is currently the main medication used in the management of symptoms associated with Parkinson's disease.


    1. Parkinson's Disease Foundation.  Understanding Parkinson's.  Accessed on May 19, 2009
    2. Shastry BS.  Parkinson's disease: etiology, pathogenesis and future gene therapy.  Neurosci Res  2001;41:5-12.  
    3. Pahwa R, Factor SA, Lyons KE et al.  Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology  2006;66:983-95.  
    4. Aminoff MJ.  Pharmacologic management of Parkinsonism & other movement disorders.  In: Basic & Clinical Pharmacology.  Katzung BG ed.  9th edition.  Lange Medical Books/McGraw-Hill.  New York, NY.  2004;447-449.
    5. Busti AJ, Lehew DS, Nuzum DS, Daves BJ, McKeever GC.  PW Pharmacother Newsl 2009;1(19):1-4.  
    6. Hashimoto W, Kitayama S, Kumagai K et al.  Transport of dopamine and levodopa and their interaction in COS-7 cells heterologously expressing monoamine neurotransmitter transporters and in monoaminergic cell lines PC12 and SK-N-SH.  Life Sci  2005;76:1603-12.  
    7. Wade LA, Katzman R.  Synthetic amino acids and the nature of L-DOPA transport at the blood-brain barrier.  J Neurochem  1975;25:837-42.

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