Levodopa-induced dyskinesia
Encyclopedia
Levodopa-induced dyskinesia is a form of dyskinesia
associated with Levodopa
used to treat Parkinson's disease
.
It has been suggested that it involves disruption of the blood brain barrier, though not all evidence supports this.
The reasons for the appearance of the dyskinesias are not entirely known, but it might be that the L-DA dose that is required to compensate for the lack of DA in striatum is above the tolerated threshold in other regions of the brain that are of importance for motor control.
In the context of Parkinson's disease
(PD), dyskinesia is often the result of chronic L-DOPA (Levodopa) therapy. These motor fluctuations occur in more than half of PD patients after 5–10 years of L-DOPA treatment, with the percentage of affected patients increasing over time. Dyskinesia most commonly occurs at the time of peak L-DOPA plasma
concentrations and is thus referred to as peak-dose dyskinesia (PDD). As patients advance, they may evidence diphasic dyskinesia (DD), which occur when the drug concentration rises or falls. Attempts to moderate dyskinesia by the use of other treatments such as bromocriptine
(Parlodel) appears to be ineffective. In order to avoid dyskinesia, patients with the young-onset form of the disease or young-onset Parkinson's disease (YOPD) are often hesitant to commence L-DOPA therapy until absolutely necessary for fear of suffering severe dyskinesia later on.
Patients with prominent dyskinesia resulting from high doses of antiparkinsonian medications may benefit from deep brain stimulation
(DBS), which benefits the patient in two ways: 1) DBS allows a reduction in L-DOPA dosage of 50-60% (thus tackling the underlying cause); 2) DBS treatment itself (in the subthalamic nucleus
or globus pallidus
) can reduce dyskinesia.
The use of MDMA ("Ecstasy") has been shown to enhance the effects of L-DOPA while reducing the associated dyskinesia in primates with advanced PD. Its serotonergic
action
s may be responsible for this effect.
Dyskinesia
Dyskinesia is a movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements, similar to tics or choreia. Dyskinesia can be anything from a slight tremor of the hands to uncontrollable movement of, most commonly, the upper body but...
associated with Levodopa
Levodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
used to treat Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
.
It has been suggested that it involves disruption of the blood brain barrier, though not all evidence supports this.
The reasons for the appearance of the dyskinesias are not entirely known, but it might be that the L-DA dose that is required to compensate for the lack of DA in striatum is above the tolerated threshold in other regions of the brain that are of importance for motor control.
In the context of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
(PD), dyskinesia is often the result of chronic L-DOPA (Levodopa) therapy. These motor fluctuations occur in more than half of PD patients after 5–10 years of L-DOPA treatment, with the percentage of affected patients increasing over time. Dyskinesia most commonly occurs at the time of peak L-DOPA plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
concentrations and is thus referred to as peak-dose dyskinesia (PDD). As patients advance, they may evidence diphasic dyskinesia (DD), which occur when the drug concentration rises or falls. Attempts to moderate dyskinesia by the use of other treatments such as bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
(Parlodel) appears to be ineffective. In order to avoid dyskinesia, patients with the young-onset form of the disease or young-onset Parkinson's disease (YOPD) are often hesitant to commence L-DOPA therapy until absolutely necessary for fear of suffering severe dyskinesia later on.
Patients with prominent dyskinesia resulting from high doses of antiparkinsonian medications may benefit from deep brain stimulation
Deep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
(DBS), which benefits the patient in two ways: 1) DBS allows a reduction in L-DOPA dosage of 50-60% (thus tackling the underlying cause); 2) DBS treatment itself (in the subthalamic nucleus
Subthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
or globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
) can reduce dyskinesia.
The use of MDMA ("Ecstasy") has been shown to enhance the effects of L-DOPA while reducing the associated dyskinesia in primates with advanced PD. Its serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...
action
Drug action
The action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins...
s may be responsible for this effect.