Carbidopa is a drug belonging to the drug group of L-DOPA decarboxylase inhibitors. The drug is used to treat Parkinson’s disease and is on the WHO essential medicines list.
What is carbidopa?
Carbidopa is a drug in the L-DOPA decarboxylase inhibitor drug group. The drug is used to treat Parkinson’s disease. Carbidopa is a selective decarboxylase inhibitor. Decarboxylase inhibitors are so-called competitive inhibitors of DOPA decarboxylase. This is an enzyme that delays the breakdown of L-dopa. L-dopa, also known as levodopa, is a substance that acts as a precursor for melanin, adrenaline, dopamine and noradrenaline. The drug was discovered in the 1950s. In 1961, 1963, 1969 and 1971 it was patented by Merck and Co. Carbidopa is usually marketed in combination with the drug levodopa. Carbidopa is used with levodopa to treat Parkinson’s disease.
Pharmacologic Action
Carbidopa selectively inhibits decarboxylase. Thus, the drug prevents the conversion of L-DOPA to dopamine in the periphery. Because carbidopa cannot cross the blood–brain barrier, the conversion of L-DOPA to dopamine in the brain is unaffected by the process.
Medical application and use
Carbidopa is used to treat Parkinson’s disease. Parkinson’s disease is a neurodegenerative disease that progresses slowly. It is characterized by the death of nerve cells in the substantia nigra in the midbrain that produce dopamine. Thus, there is a deficiency of the neurotransmitter dopamine and ultimately a reduction in the activating effect of the basal ganglia on the cortex of the cerebrum. Leading symptoms of Parkinson’s disease are muscle rigidity (rigor), slowed movements, muscle tremors, immobility and postural instability. Treatment of PD is usually with L-DOPA preparations. L-DOPA is a precursor in the biosynthesis of dopamine. After passing the blood–brain barrier, L-DOPA is metabolized in the brain to dopamine. This develops the desired pharmacological effect and leads to symptom relief. Levodopa thus belongs to the group of so-called prodrugs. However, to prevent the substance from being metabolized in the periphery, the L-DOPA decarboxylase inhibitor carbidopa is used. Without the inhibition of decarboxylation in the periphery by carbidopa, 95 percent of the administered L-DOPA would already be metabolized outside the brain. By additionally administering carbidopa, the dose of L-DOPA can be reduced. Thus, there are also fewer side effects. Patients receiving a combination of L-DOPA and carbidopa are less likely to suffer from nocturia, tachycardia, or orthostatic dysregulation.
Risks and Side Effects
However, side effects can also result from taking carbidopa. For example, nausea and vomiting may occur. Schizophrenia-like symptoms are also observed. Here, a distinction can be made between positive and negative symptoms. The positive symptoms occur quasi in addition to the normal personality. These include delusions, thought disorders, and ego disorders. Negative symptoms affect drive, psychomotor function, thinking, and affect. Affect impoverishment develops. The ability to experience emotions is reduced. The psychomotor activity of the affected person is reduced. The facial expressions and gestures of the patients appear rigid. The drive is also diminished. Thinking is empty, unimaginative and impoverished. Often, these symptoms are complemented by cognitive impairment. In addition to schizophrenia-like symptoms, sufferers may also be confused or exhibit nightmares. Sleep disturbances, may also occur acutely. With continuous medication, akinesia may develop. Akinesia is a pathological lack of movement. This phenomenon is also known as end-of-dose akinesia in PD. Here, the loss of movement occurs at the end of the duration of action of a dose of the Parkinson’s drug taken. Another side effect of long-term medication with carbidopa is freezing. In neurology, the term freezing refers to sudden blockages in movement. Patients freeze in mid-motion and are unable to move. Furthermore, paroxysmal on/off phenomena may occur.The on/off phenomenon is characterized by sudden changes from good mobility to absolute immobility. The phenomena can last from minutes to hours. The exact cause has not yet been determined. Furthermore, hyperkinesia and dyskinesia may develop with prolonged use of carbidopa. In hyperkinesia, mobility is pathologically increased. This manifests as involuntary, sudden, and unpredictable movements of the face, trunk, neck, or extremities. Dyskinesia is also a disturbance of normal movement. In PD, dyskinesias appear as involuntary over-movements. Caution is advised when combining levodopa and carbidopa with tricyclic antidepressants. Here, in individual cases, a life-threatening drop in blood pressure occurs. In contrast, a crisis-like rise in blood pressure can develop in combination with drugs from the MAO inhibitor group. It should be noted that metoclopramide accelerates gastric emptying and thus increases the effect of carbidopa and levodopa. Simultaneous ingestion of a high-protein meal may decrease the effect of the combination drug. The same applies to the simultaneous use of iron preparations. Iron preparations should therefore always be taken at least two hours before or at least two hours after administration of the drug combination.
