Use of a single anti-parkinson’s medication as primary treatment to control the symptoms of Parkinson’s. A common monotherapy is the Levodopa, which the brain metabolizes (converts) to dopamine. This process provides a temporary replacement supply of dopamine to compensate for the depletion that occurs as a result of the death of dopaminergic neurons. As Parkinson’s progresses and dopaminergic neurons continue to die higher dosages of levodopa are required to achieve symptom relief. As well, dopamine receptors become less responsive (sensitized) and require higher amounts of dopamine for activation.
Sometimes other anti-Parkinson’s medications are effective as monotherapy early in the course of the disease, particularly with de novo Parkinson’s (Parkinson’s that is newly diagnosed and has never been treated). These include
• amantadine. This antiviral medication was developed in the 1960s to shorten the course of influenza A. It also has central dopamine agonist action and can cross the blood-brain barrier. Although researchers do not know its precise mechanisms, amantadine either stimulates dopaminergic neurons to increase dopamine production or activates dopamine receptors in ways that simulate the action of dopamine. Amantadine monotherapy can delay the need for levodopa for up to two years; much longer delays are possible if dopamine agonists can be added first.
• dopamine agonists. These medications are chemically similar to dopamine and can bind with, or activate, dopamine receptors in the brain. They, like amantadine, are able to cross the blood-brain barrier. Because they do not have exactly the same molecular configuration as dopamine, dopamine agonists bind incompletely but enough to “bridge” neuron communication as a supplement to endogenous dopamine. The action is analogous to decoding word messages when the vowels are missing. As dopamine levels continue to decline with the progression of Parkinson’s, the limitations of this incomplete binding become more pronounced and the “bridge” carries less of the neuron mes-sages—not enough gets through to deliver coherent communication. To extend the word messages analogy, consonants drop out as well as vowels, leaving inadequate clues for deciphering the words. common dopamine agonists are bromocriptine, pergolide, pramipexole, and ropinirole. The latter two of these, which target specific dopamine receptors (D2, D3, D4), show promise of being as effective as levodopa in early Parkinson’s and can postpone the need for levodopa for up to three to five years on average, with some people being able to be maintained on dopamine agonist monotherapy for over a decade.
• Monoamine oxidase inhibitor-type B (MAOI-B): monoamine oxidase (MAO) is an enzyme that initiates metabolism of monoamine neurotransmitters. Monoamine oxidase type B (MAO-B) specifically targets dopamine. Inhibiting, or blocking, the action of MAO-B extends the availability of dopamine in the brain and thereby sometimes relieves the neuromuscular symptoms in early Parkinson’s. The only MAO-B inhibitor medication available in the United States at present is selegiline (Deprenyl). It can postpone the need for levodopa for up to three years. Rasaligine, an MAO-B inhibitor that has undergone testing in people with Parkinson’s, may be approved soon and has data that mainly supports its use as an adjunct therapy in people with moderate to severe Parkinson’s.
There is debate among specialists who treat people with Parkinson’s about how long to delay levodopa therapy by use of other anti-Parkinson’s medications during the disease’s early stages. virtually all neurologists believe when symptom control is as effective, and side effects are not any higher, with another medication as monotherapy, delaying levodopa therapy is worthwhile. it is important to note that the listed alternative monotherapies to levodopa all pose a significantly greater risk of worsening cognition in elderly or cognitively impaired people than levodopa. What is more difficult to determine is when the less complete symptom control or more problematic side effects of other monotherapies reach the point that they unfavorably compare to the known risks of motor complications—and some possible theoretical risk of contributing to disease progression—which initiation of levodopa therapy engenders. Medications other than levodopa that are taken as monother-apy early in the course of Parkinson’s typically remain effective later in the disease as adjunct therapies, when they are able to supplement and extend the effectiveness of levodopa.
