Physicians can use different combinations of the many available medical strategies 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 and cost.
Blockers and Inhibitors
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 drugs 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®)
- Carbidopa/Levodopa + Entacapone (Stalevo®)
- Tolcapone (Tasmar®) Tolcapone unlike entacapone, (Comtan®) can cross the blood brain barrier and inhibit COMT in both the peripheral and central nervous systems.
Tasmar® 100 mg
Tasmar® 200 mg
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).
- Selegiline (Eldepryl®) Eldepryl®100 mg
- Selegiline HCL Orally disintegrating (Zelepar®) Zelepar®1.25 mg
- Rasagiline (Azilect®) Azilect®1.0 mg, Azilect®.05 mg
Anticholinergic drugs were the original line of drugs used to treat PD. Now they are infrequently used for mild (tremor predominant) PD symptoms and in attempt to restore balance. This class of drugs act on acetylcholine system to balance out dopamine production Acetylcholine transmitters act on skeletal muscles. When they bind to the receptor sites on the muscle, their affect is to contract or shorten the muscle. Anticholinergics block the acetylcholine transmitter receptor sites on the muscle which in turn inhibits the transmission resulting in the relaxation or lengthening of the muscle.
- Benzotropine mesylate (Cogentine®) is used to control tremors and stiffness of the muscles. Long duration of action of this drug makes it particularly suitable for bedtime medication when its effects may last throughout the night.
- Trihexyphenidyl HCL (Artane®) Artane can help decrease muscle stiffness, sweating, and the production of saliva, and helps improve walking ability in people with PD. Artane may not work as well and may require different dosing when used for an extended period
- Amantadine HCL (Symmetrel®) Some symptomatic benefit may result in the use of amantadine, including smoothing out the motor fluctuations which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of amantadine.
Dopamine Supplementation or Augmentation
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. Dopamine agonist therapy “mimics” the affect of 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®)
Recently approved by the FDA in a Controled Release form
- Ropinerole (Requip®)
Now available in Generic Form
- Ropinerole (Requip XL®) Extended Release
Requip XL®2.0 mg
Requip XL®4.0 mg
Requip XL®8.0 mg
- Apomorphine Hydrocloride injection (Apokyn®)
Common treatments for motor symptoms of Parkinson disease
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 was developed in the mid 1960’s and still remains the “gold standard” in treating the symptoms.
The addition of carbidopa prevents levodopa from being broken down in the blood stream before entering the brain. By inhibiting the breakdown of L-dopa, it increases the amount of dopamine available to the motor neurons which in turn reduces the movement disorder symptoms. Additionally it greatly reduces the nausea associated with the byproduct resulting from the breakdown of levodopa.
- Carbidopa/Levodopa (Sinemet®)
Sinemet CR®25/100 (Controlled Release)
Sinemet CR®25/250 (Controlled Release)
Generic Carbidopa/Levodopa in immediate release form is available from a number of manufactures in the same dosages.
- Carbidopa/Levodopa orally disintegrating (Parcopa®)
Parcopa® 10/100 mg
Parcopa® 25/100 mg
Parcopa® 25/250 mg
Now avialable in Generic Form in same dosage
- Carbidopa/Levodopa+Entacapone (Stalevo®)