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TREATMENTS OF PARKINSON'S DISEASE

 

 
 

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 body's own formation of L-dopa. By this means L-dopa eventually becomes counterproductive.

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. For more details go to Sinemet and Sinemet CR

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. For more details go to Madopar and Madopar CR

PARCOPA consists of L-dopa and Carbidopa, the same as Sinemet, but is in orally disintegrating tablets. For more details go to Parcopa

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. For more details go to Duodopa

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

MUCUNA PRURIENS is a natural vegetable source of therapeutic quantities of L-dopa. For more details go to Mucuna pruriens

 

DOPAMINE AGONISTS

Dopamine agonists are drugs that mimic dopamine by stimulating the dopamine receptors. Besides the side effects they cause, dopamine agonists cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms. The most widely used dopamine agonists include :

APOMORPHINE (which is sold as Apokyn) is taken via injection or infusion. For more details go to Apokyn

BROMOCRIPTINE (which is sold as Parlodel). For more details go to Parlodel

CABERGOLINE (which is sold as Dostinex and Cabaser). For more details go to Dostinex

PRAMIPEXOLE (which is sold as Mirapex and Mirapex ER). For more details go to Mirapex and Mirapex ER

ROPINIROLE (which is sold as Requip and Requip XL). For more details go to Requip and Requip XL

ROTIGOTINE (which is sold as Neupro) is applied using a transdermal patch. For more details go to Neupro

 

MAO-B INHIBITORS

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. MAO-B inhibitors cause widespread side effects. The most common MAO-B inhibitors are :

SELEGILINE (which is sold as Eldepryl). For more details go to Eldepryl 

RASAGILINE (which is sold as Azilect). For more details go to Azilect

 

ANTI-MUSCARINICS (ANTI-CHOLINERGICS)

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.  Anti-Muscarinics are found in natural sources such as the highly poisonous plant Deadly Nightshade. Anti-Muscarinics cause very widespread side effects and so are not so commonly used.  The anti-muscarinics include :

BENZTROPINE (which is sold as Benztropine mesylate and Cogentin, which is injectable)  For more details go to Benztropine mesylate  and Cogentin

TRIHEXYPHENIDYL (which is sold as Artane) For more details go to Artane

BIPERIDEN (which is sold as Akienton) For more details go to Akineton

PROCYCLIDINE (which is sold as Kemadrin) For more details go to Kemadrin

 

NUTRITIONAL TREATMENTS

DOPAVITE is a nutritional supplement that contains all of the nutrients required for dopamine formation. It can be used alongside all other products for Parkinson's Disease in order to supplement their effect. For more details go to Dopavite

VITAMIN C AND VITAMIN E usually in combination and 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. For more details go to Coenzyme Q10  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. For more details go to MitoQ

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. For more details go to Glutathione

 

SURGICAL TREATMENTS

DEEP BRAIN STIMULATION (DBS) involves the use of electrodes that are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS can reduce the need for L-dopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of L-dopa. It helps to alleviate fluctuations of symptoms and reduce tremors, slowness of movements, and gait problems. DBS requires careful programming of the stimulator device. For more information go to Deep brain stimulation

GENE THERAPY is currently under investigation. It involves using a harmless virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor on the overactive cells in the STN. For more information go to Gene therapy                    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.

 

TECHNOLOGICAL DEVICES

FOCUSED ULTRASOUND is an incisionless method of thalamotomy for people who are not candidates for surgery or who do not want to undergo an invasive procedure. Multiple intersecting beams of ultrasound energy are focused with a high degree of precision and accuracy on the target in the thalamus. For more information go to Focused Ultrasound.

FUNCTIONAL ELECTRICAL STIMULATION is The use of electrical impulses to stimulate weak or paralysed muscles, called Functional Electrical Stimulation (FES), is often used to help stroke or multiple sclerosis patients to walk [1]. Many people with Parkinsonís are prone to tripping and falling because they have difficulty picking up their feet consistently. They also can have difficulty with starting and maintaining walking. This study aimed to investigate the effect of Functional Electrical Stimulation (FES) on walking ability in people with Parkinson's disease.

 

PHYSICAL THERAPY

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

Light therapy or phototherapy consists of exposure to specific wavelengths of light using lasers, LEDs, fluorescent lamps, dichroic lamps or very bright, full-spectrum light, for a prescribed amount of time. For more information got to Bright light therapy. Light therapy has been used to reduce Parkinson's Disease symptoms. For more information got to the Complete abstract. Light suppresses melatonin formation, which in turn lowers dopamine activity. As a lack of dopamine causes Parkinson's Disease, light is used to suppress the interfering effect of melatonin.

 

Electromagnetic stimulation

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.

 

 

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