L-DOPA

The most widely used form of treatment is L-dopa in various forms. L-dopa is transfomed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase (often known by its former name dopa-decarboxylase). However, only 1-5% of L-DOPA enters the dopaminergic neurons. The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so L-dopa eventually becomes counterproductive. Mucuna pruriens is a natural source of therapeutic quantities of L-dopa.

Sinemet consists of L-dopa and Carbidopa (a dopa decarboxylase inhibitor that  helps to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons). There is also a controlled release version, Sinemet CR, that spreads out the effect of the L-dopa.

Madopar consists of L-dopa and Benserazide (a dopa decarboxylase inhibitor that helps to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons). There is also a controlled release version called Madopar CR that spreads out the effect of L-dopa.

Parcopa consists of L-dopa and Carbidopa, the same as Sinemet, but is in orally disintegrating tablets.

Duodopa is a combination of L-dopa and Carbidopa, dispersed as a viscous gel. Using a patient-operated portable pump, the drug is continuously delivered via a tube directly into the upper small intestine, where it is rapidly absorbed.

Stalevo consists of L-dopa, Carbidopa and Entacopone (Comtan). Entacapone (Comtan) inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa.  Tolcapone does the same, but can have serious side effects.

DOPAMINE AGONISTS

Dopamine agonists are drugs that mimic dopamine by stimulating the dopamine receptors. The dopamine agonists include Bromocriptine (Parlodel), Pramipexole (Mirapex), Ropinirole (Requip), Cabergoline (Dostinex, Cabaser), Lisuride (Revanil), Rotigotine (Neupro) which is applied using a transdermal patch, and Apomorphine hydrochloride (Apokyn) which is administered via injection or infusion. Pergolide (Permax) has been widely withdrawn from use. Besides the side effects they cause, dopamine agonists cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.

MAO-B inhibitors do not directly increase the formation of dopamine or its activity. MAO-B inhibitors instead reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. The most common MAO-B inhibitors are Selegiline  (Eldepryl) and Rasagiline (Azilect). MAO-B inhibitors cause widespread side effects.

The excessive muscle contraction in Parkinson's Disease is caused when the cholinergic function (which increases muscle contraction) is more powerful than dopaminergic function (which decreases muscle contraction). Instead of increasing dopaminergic function which is what most treatments of Parkinson's Disease aim at achieving, Anti-muscarinics reduce cholinergic function. Several drugs in this category sometimes help relieve symptoms, particularly tremor. The anti-muscarinics include : Benztropine mesylate (Cogentin), Trihexyphenidyl hydrochloride (Artane), Biperiden hydrochloride (Akineton), Orphenadrine citrate (Biorphen, Disipal), and Procyclidine Hydrochloride (Kemadrin). Anti-Muscarinics cause very widespread side effects.   Anti-Muscarinics are found in natural sources such as the highly poisonous plant Deadly Nightshade.

Amantadine hydrochloride (Symmetrel) can be used as monotherapy in early Parkinson's Disease, for tremor or bradykinesia, but has a weak and short-lived benefit.

Dopavite is a nutritional supplement that contains all of the nutrients required for dopamine formation, that can be used alongside all other products for Parkinson's Disease either as a replacement or in order to supplement their effect.

Vitamin C and Vitamin E, usually in combination in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in Parkinson's disease. This is because the enzymes superoxide dismutase and catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly produced in damaged cells.

Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to Coenzyme Q10. However, proof of benefit has not yet been demonstrated.

Glutathione is a naturally occurring combination of three amino acids. It is most effectively administered intravenously. Glutathione is an antioxidant, but also facilitates entry of the dopamine precursors in to the dopaminergic neurons.

GDNF therapy is still being developed. It involves, by surgical means, the infusion of GDNF (glial-derived neurotrophic factor) into the basal ganglia using implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa.

Stem cell therapy is still under investigation. Initial results have not been impressive. It involves the implantation in to the brain of cells that are able to produce dopamine. This method could not constitute a cure because it does not address the considerable loss of activity of the enzymes involved in dopamine formation.

Spheramine Spheramine is a standardized cell therapy using normal human cells. These cells, retinal pigment epithelial (RPE) cells, are placed on microcarriers and injected into the brain to provide a localized continuous source of dopamine in brain regions deficient in dopamine. This method is still in development.

Pallidotomy, Thalamotomy and Subthalamotomy, involve the removal of a small part of three target locations : the Globus pallidum internus (Pallidotomy), the Thalamus (Thalamotomy),  and the Subthalamic nucleus (Subthalamotomy). Pallidotomy has been used for unilateral dyskinesia, severe on/off fluctuations and drug failure. Thalamic surgery has been used as a means of controlling tremor but has no effect on bradykinesia. Subthalamic surgery is used to improve tremor, bradykinesia and rigidity but may provoke dyskinesias and hemiballismus.

Regular physical exercise and/or physical therapy, including EECP are often used in Parkinson's Disease for maintaining and improving mobility, flexibility, balance and a range of motion. The goal of therapy has been largely to help people maintain what motor capability they have for as long as possible and to help them adjust as their functional level declines. Although the short term effect of physical exercise can be to increase muscle contraction and thereby exacerbate symptoms, the long term effect is the reduction in muscle contraction. Alternative forms of physical exercise such as yoga, tai chi, and dance can also be beneficial to the patient.

BRIGHT LIGHT THERAPY

Transcranial magnetic stimulation is a non-invasive method of exciting neurons. The excitation is caused by weak electric currents induced in the tissue by rapidly changing magnetic fields (electromagnetic induction). This way, brain activity can be triggered or modulated without the need for surgery or external electrodes. For more information on  Transcranial magnetic stimulation . Light therapy has been used to reduce Parkinson's Disease symptoms. For more information go to the Complete abstract.