What is the goal of pharmacological (pharm) therapy in Parkinson's disease, specifically in terms of balancing cholinergic and dopaminergic activity in the brain?

From the Guidelines

The primary goal of pharmacological therapy in Parkinson's disease is to balance cholinergic and dopaminergic activity in the brain by increasing dopaminergic activity and reducing relative cholinergic excess. This balance is crucial because Parkinson's disease results from a deficiency of dopamine in the basal ganglia, creating an imbalance where cholinergic activity becomes relatively excessive. The primary approach involves increasing dopaminergic activity through medications like levodopa (usually combined with carbidopa to prevent peripheral conversion), dopamine agonists (such as pramipexole 1), and MAO-B inhibitors. Some patients may also benefit from anticholinergic medications which reduce the relative cholinergic excess, though these are used less frequently due to side effects, especially in older patients.

Key considerations in managing Parkinson's disease include:

• Starting treatment with dopamine agonists in younger patients and levodopa in older patients
• Adjusting medications based on symptom control and side effects
• Using COMT inhibitors to extend levodopa's effectiveness
• Being cautious with the use of dopaminergic agonists in patients who may develop neurodegenerative diseases like dementia with Lewy bodies, as they may exacerbate symptoms 1.

The aim of this pharmacological approach is to restore the neurotransmitter balance, improving motor symptoms like tremor, rigidity, and bradykinesia that result from the disrupted equilibrium between these two neurotransmitter systems, ultimately reducing morbidity, mortality, and improving quality of life for patients with Parkinson's disease.

From the FDA Drug Label

The mechanisms accounting for selegiline’s beneficial adjunctive action in the treatment of Parkinson’s disease are not fully understood. Inhibition of monoamine oxidase, type B, activity is generally considered to be of primary importance; in addition, there is evidence that selegiline may act through other mechanisms to increase dopaminergic activity Many of the prominent symptoms of Parkinson’s disease are due to a deficiency of striatal dopamine that is the consequence of a progressive degeneration and loss of a population of dopaminergic neurons which originate in the substantia nigra of the midbrain and project to the basal ganglia or striatum MAO-B inhibition may be useful in this setting because, by blocking the catabolism of dopamine, it would increase the net amount of dopamine available (i.e., it would increase the pool of dopamine)

The goal of pharmacological therapy in Parkinson's disease, specifically in terms of balancing cholinergic and dopaminergic activity in the brain, is to increase dopaminergic activity. This can be achieved through MAO-B inhibition, which blocks the catabolism of dopamine and increases the net amount of dopamine available. However, the exact mechanisms by which selegiline exerts its beneficial effects are not fully understood 2 2.

• Key points:
  • Inhibition of monoamine oxidase, type B, activity is considered to be of primary importance
  • Selegiline may act through other mechanisms to increase dopaminergic activity
  • The goal is to increase the net amount of dopamine available in the brain
• Main idea: The goal of pharmacological therapy in Parkinson's disease is to increase dopaminergic activity, primarily through MAO-B inhibition.

From the Research

Pharmacological Therapy in Parkinson's Disease

The goal of pharmacological therapy in Parkinson's disease is to balance cholinergic and dopaminergic activity in the brain.

• Dopaminergic therapy is the primary approach, focusing on replacing dopamine or stimulating dopamine receptors to alleviate symptoms 3, 4, 5.
• Dopaminergic agents, such as levodopa and dopamine receptor agonists, are used to improve motor function and reduce symptoms 4, 6.
• Anticholinergic drugs may be used in specific situations, such as to treat tremors or rigidity, by blocking the action of acetylcholine and balancing cholinergic activity 7.
• The current treatment concept is continuous dopaminergic stimulation (CDS), which aims to provide stable plasma concentrations of levodopa and reduce fluctuations in motor performance 6.

Balancing Cholinergic and Dopaminergic Activity

• The pharmacologic management of Parkinson's disease is limited primarily to manipulation of the dopamine-acetylcholine system 7.
• Levodopa, with or without a peripheral dopa decarboxylase inhibitor, is the current drug of choice in the management of idiopathic and postencephalitic Parkinson's disease, and works by increasing dopaminergic activity 7.
• Anticholinergics and antihistamines are the agents of choice for neuroleptic-induced Parkinson's disease, and work by reducing cholinergic activity 7.
• Modification of the serotonin-histamine system via the use of antihistamines may be useful in some patients, and can help balance cholinergic and dopaminergic activity 7.