Physicians can use different medications and combinations of available medications based on the needs of each patient and physicians' treatment philosophy. Considerations related to the choice of medications include efficacy for symptomatic control, side effects, safety, practicality, cost and sensitivities of their individual patients.
Dopamine Replacement Therapy
Although the dopamine deficiency causes the motor problems associated with PD, dopamine cannot cross the blood brain barrier (moving from the blood stream into the brain) and therefore it can’t be directly used as a medication to treat the disease. Levodopa is a precursor of the dopamine neurotransmitter and can be converted to dopamine once inside the brain.
Carbidopa/Levodopa: Levodopa is the gold standard medication for PD with the broadest antiparkinsonian effects of any treatment. In the brain, neurons typically convert levodopa to dopamine. Levodopa works by replacing the dopamine lost in PD. It is combined with carbidopa to ensure levodopa is not metabolized before it enters the brain and in turn prevents nausea that can accompany the breakdown.
- Immediate Release Carbidopa/Levodopa
Dosage (in mg):
- Controlled or Extended Release Carbidopa/Levodopa
Dosage (in mg):
Sinemet CR®25/100 (Controlled Release)
Sinemet CR®25/250 (Controlled Release)
- Enteral Suspension Continuous Infusion (Duopa™)
Continuous infusion of carbidopa/levodopa into the small intestine via pump and tube
Dosage (in mg):
Dopamine Agonists: Dopamine agonists are drugs that stimulate the parts of the human brain that are influenced by dopamine. In effect, the brain is tricked into thinking it is receiving the dopamine it needs. Dopamine Agonist therapy does not replace dopamine; it makes the existing dopamine more effective by binding to the same receptor sites on the neurons normally occupied by dopamine. These agonist stimulated neurons require less dopamine to complete the neural transmission.
Dopamine agonists can be taken alone (mono- therapy) or in combination with medications containing levodopa (adjunctive therapy)
- Pramipexole (Mirapex®)
- Ropinerole (Requip®)
- Ropinerole Extended Release (Requip XL® and generic)
- Apomorphine Hydrocloride injection (Apokyn®)
These types of drugs block or inhibit the breakdown of levodopa or dopamine which in turn helps maintain dopamine levels in the motor neurons
Catecholamine-O-Methyltransferase (COMT) Inhibitor
COMT breaks down levodopa in the bloodstream reducing the amount that is able to cross the blood brain barrier to become available for conversion into dopamine in the brain. This class of drug blocks the action of the COMT enzyme which in turn maintains a higher level of L-dopa resulting in an increased the amount of dopamine (similar to action of carbidopa).
There are two types of COMT Inhibitors used in Parkinson's disease
- Entacapone cannot cross the blood-brain barrier, and only works peripherally
- Tolcapone can cross the blood brain barrier and prevents the breakdown of both dopamine and L-dopa by COMT enzymes in both the central and peripheral nervous system
Both must be taken with taken with levodopa in order for it to work
- Entacapone (Comtan®)
- Tolcapone (Tasmar®)
Monoamine Oxidase B (MOAB) Inhibitors
When released dopamine is not used (bound) in the transmission of the message, it can be taken back up into the releasing neuron. Monoamine Oxidase (MOA)is an enzyme that breaks down dopamine in the neuron (outside of the storage vesicles) to keep dopamine levels in the storage vesicles from over capacity. MAO-B (B is the type of receptor) inhibitors, bind to and inhibit the MAOB enzyme from breaking down dopamine. Prolonged use may enhance release of dopamine. MAOB Inhibitors can be taken alone (mono- therapy) or in combination with medications containing levodopa (adjunctive therapy).
- Rasagiline (Azilect®)
Azilect®1.0 mg, Azilect®.05 mg
- Selegiline (Eldepryl®)
- Selegiline HCL Orally disintegrating (Zelepar®)
Anticholinergics do not act directly on the dopaminergic system. Instead, they decrease the activity of acetylcholine, a neurotransmitter that regulates movement and memory.
Amantadine (Symmetrel™) promotes the release of dopamine from nerve terminals, blocks its re-uptake and inhibits a glutamate receptor in the brain. It may decrease the activity of acetylcholine, which regulates movement and memory.
Droxidopa (Northera™) is a synthetic precursor of norepinephrine, which works to increase blood pressure in a condition that can accompany Parkinson’s disease called neurogenic orthostatic hypotension (NOH). This condition can cause an abnormal drop in blood pressure when changing positions.
Pimavanserin (Nuplazid™) only medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis.