Combination of | |
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Carbidopa | DOPA decarboxylase inhibitor |
Levodopa | dopamine precursor |
Entacapone | catechol-O-methyltransferase inhibitor |
Clinical data | |
Trade names | Stalevo, Corbilta, Carlevent |
AHFS/Drugs.com | Professional Drug Facts |
MedlinePlus | a601068 |
License data | |
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Routes of administration | By mouth |
ATC code | |
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PubChem CID | |
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Carbidopa/levodopa/entacapone, sold under the brand name Stalevo among others, is a dopaminergic fixed-dose combination medication that contains carbidopa, levodopa, and entacapone for the treatment of Parkinson's disease. [5]
Carbidopa/levodopa/entacapone is indicated for the treatment of Parkinson's disease. [5]
In the European Union it is indicated for the treatment of adults with Parkinson's disease and end-of-dose motor fluctuations not stabilized on levodopa/dopa decarboxylase (DDC) inhibitor treatment. [6]
Sometimes a wearing off effect may occur at the end of the dosing interval, where a patient may feel Parkinson's symptoms. Urine, saliva, or sweat may be discolored (dark color such as red, brown, or black) after taking carbidopa/levodopa/entacapone. [8]
Carbidopa/levodopa/entacapone is contraindicated in patients taking a class of antidepressant drugs known as non-selective monoamine oxidase (MAO) inhibitors such as phenelzine and tranylcypromine. [9]
Carbidopa/levodopa/entacapone may be combined with the drugs rasagiline or selegiline. These drugs are a different type of MAO inhibitor known as selective MAO inhibitors that are often prescribed for Parkinson's disease. [8] Many drug interactions involving selegiline are theoretical, primarily based on interactions with non-selective MAO inhibitors; at oral doses the risk of these interactions may be very low. However, transdermal selegiline, known by its trade name Emsam, is still contraindicated. [9] Transdermal selegiline results in higher plasma levels at which it behaves like a non-selective MAO inhibitor. Concominant use of entacapone, a component of carbidopa/levodopa/entacapone, with MAO inhibitors may increase toxicity of MAO inhibitors. Levodopa, also a component of carbidopa/levodopa/entacapone, in combination with MAO inhibitors may result in hypertensive reactions. [10]
Levodopa is the immediate precursor to dopamine. Entacapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor that prevents the degradation of levodopa. Entacapone does not cross the blood–brain barrier. Carbidopa is a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor. Carbidopa, which also does not cross the blood–brain barrier, is combined with levodopa to prevent its conversion to dopamine in the periphery. [11] [ unreliable medical source? ]
Carbidopa/levodopa/entacapone was approved by the US Food and Drug Administration (FDA) in June 2003. [12] [13]
It may help decrease a change of response to Parkinson's medications. [14]
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
ATC code N04Anti-parkinson drugs is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup N04 is part of the anatomical group N Nervous system.
l-DOPA, also known as levodopa and l-3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize l-DOPA, make it via biosynthesis from the amino acid l-tyrosine. l-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, l-DOPA itself mediates neurotrophic factor release by the brain and CNS. l-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.
Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–brain barrier for central nervous system effect, instead of being peripherally metabolised into substances unable to cross said barrier.
Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth or orally disintegrating tablets taken on the tongue for Parkinson's disease and as a patch applied to skin for depression.
Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.
Carbidopa/levodopa, also known as levocarb and co-careldopa, is the combination of the two medications carbidopa and levodopa. It is primarily used to manage the symptoms of Parkinson's disease, but it does not slow down the disease or stop it from getting worse. It is taken by mouth. It can take two to three weeks of treatment before benefits are seen. Each dose then begins working in about ten minutes to two hours with a duration of effect of about five hours.
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.
Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of Parkinson's disease. Entacapone together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson's disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone.
Tolcapone, sold under the brand name Tasmar, is a medication used to treat Parkinson's disease (PD). It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-O-methyltransferase (COMT). It has demonstrated significant liver toxicity, which has led to suspension of marketing authorisations in a number of countries.
Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.
In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. At present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms.
A catechol-O-methyltransferase(COMT) inhibitor is a drug that inhibits the enzyme catechol-O-methyltransferase. This enzyme methylates catecholamines such as dopamine, norepinephrine and epinephrine. It also methylates levodopa. COMT inhibitors are indicated for the treatment of Parkinson's disease in combination with levodopa and an aromatic L-amino acid decarboxylase inhibitor. The therapeutic benefit of using a COMT inhibitor is based on its ability to prevent the methylation of levodopa to 3-O-methyldopa, thus increasing the bioavailability of levodopa. COMT inhibitors significantly decrease off time in people with Parkinson's disease also taking carbidopa/levodopa.
Istradefylline, sold under the brand name Nourianz, is a medication used as an add-on treatment to levodopa/carbidopa in adults with Parkinson's disease (PD) experiencing "off" episodes. Istradefylline reduces "off" periods resulting from long-term treatment with the antiparkinson drug levodopa. An "off" episode is a time when a patient's medications are not working well, causing an increase in PD symptoms, such as tremor and difficulty walking.
Droxidopa is a synthetic amino acid precursor which acts as a prodrug to the neurotransmitter norepinephrine (noradrenaline). Unlike norepinephrine, droxidopa is capable of crossing the protective blood–brain barrier (BBB).
An aromatic L-amino acid decarboxylase inhibitor is a medication of type enzyme inhibitor which inhibits the synthesis of dopamine by the enzyme aromatic L-amino acid decarboxylase. It is used to inhibit the decarboxylation of L-DOPA to dopamine outside the brain, i.e. in the blood. This is primarily co-administered with L-DOPA to combat Parkinson's disease. Administration can prevent common side-effects, such as nausea and vomiting, as a result of interaction with D2 receptors in the vomiting center located outside the blood–brain barrier.
Safinamide is a drug used as an add-on treatment for Parkinson's disease with "off" episodes; it has multiple modes of action, including the inhibition of monoamine oxidase B.
Pimavanserin, sold under the brand name Nuplazid, is an atypical antipsychotic which is approved for the treatment of Parkinson's disease psychosis and is also being studied for the treatment of Alzheimer’s disease psychosis, schizophrenia, agitation, and major depressive disorder. Unlike other antipsychotics, pimavanserin is not a dopamine receptor antagonist.
Opicapone, sold under the brand name Ongentys, is a medication which is administered together with levodopa in people with Parkinson's disease. Opicapone is a catechol-O-methyltransferase (COMT) inhibitor.
Monoamine precursors are precursors of monoamines and monoamine neurotransmitters in the body. The amino acids L-tryptophan and L-5-hydroxytryptophan are precursors of serotonin and melatonin, while the amino acids L-phenylalanine, L-tyrosine, and L-DOPA (levodopa) are precursors of dopamine, epinephrine (adrenaline), and norepinephrine (noradrenaline). Administration of monoamine precursors can increase the levels of monoamine neurotransmitters in the body and brain. Monoamine precursors may be used in combination with peripherally selective aromatic L-amino acid decarboxylase inhibitors such as carbidopa and benserazide. Carbidopa/levodopa is used to increase brain dopamine levels in the treatment of Parkinson's disease while carbidopa/oxitriptan (EVX-101) is under development as an antidepressant for possible use in the treatment of depression.