Comparison of Dopamin Level in Idiopathic Parkinson's Patients

After more than 40 years of routine clinical use, levodopa has remained the gold standard of symptomatic efficacy in the treatment of Parkinson's disease (PD). Levodopa benserazide and levodopa carbidopa entacapone are antiparkinsonian agents used to treat the motor symptoms of Parkinson's disease.

Parkinson's disease is a neurodegenerative disease characterized by the loss of dopamine-producing neurons in the brain. Dopamine is a neurotransmitter that is central to controlling movement in the brain. Dopamine deficiency leads to motor symptoms typical of Parkinson's disease. These symptoms are tremor, rigidity, bradykinesia and postural instability. Levodopa is an amino acid that is the precursor of dopamine. When levodopa reaches the brain, it participates in dopamine synthesis and increases dopaminergic activity. Levodopa is the most effective agent in treating the motor symptoms of Parkinson's disease. However, chronic use of levodopa can lead to motor complications. These may include end-of-dose worsening, motor fluctuations and dyskinesias. These complications are due to levodopa's short half-life and pulsatile stimulation of striatal dopamine receptors. A dopa decarboxylase inhibitor (DDCI) is added to levodopa to reduce the peripheral metabolism of levodopa and prevent nausea. These inhibitors may be carbidopa or benserazide. The main peripheral pathway of metabolism of levodopa given with DDCI is the catechol-O-methyl transferase (COMT) enzyme. Entacapone, a drug that inhibits the COMT enzyme, can also be added to the levodopa/DDCI combination. Entacapone prolongs the peripheral half-life of levodopa and increases its central bioavailability.

Levodopa is always combined with a dopa-decarboxylase inhibitor (DDCI), and available preparations use either carbidopa or benserazide to block the main levodopa-metabolizing enzyme. Previous randomized, controlled studies in PD patients reported that clinical effects and levodopa pharmacokinetics (PK) were comparable between carbidopa and benserazide.

Levodopa benserazide and levodopa carbidopa entacapone combinations are effective and safe antiparkinson agents in treating motor symptoms in Parkinson's disease. These drugs increase ON-time and decrease OFF-time in Parkinson's disease patients and provide symptomatic relief. In some selected patients with advanced stages and dyskinesia, levodopa carbidopa can be used in device-assisted treatments in the form of intestinal gel.

Apart from levodopa preparations, it is widely used in preparations containing rasagiline in our country as a monoamine oxidase (MAO) inhibitor in Parkinson's patients. Apart from this, another group of drugs aimed at reducing symptoms in young patients are drugs called dopamine agonists, which are given to the body to synthesize dopamine. Among these treatments, pramipexole, ropirinol and apomorphine, which can be given with device support or given by subcutaneous injection, are used in our country. Deep brain stimulation, also known as brain stimulation, is another treatment method applied to invasive selected patients.

MAO inhibitors, dopamine agonists, levodopa preparations or deep brain stimulation can be used alone or in combination, depending on patient characteristics. Parkinson's disease is a progressive disease in nature, and difficulties arise in the management of patients over the years. The most common side effects are that treatments given to patients at advanced stages do not provide the expected benefit or dyskinesia occurs. The reason for this may be related to the progression of destruction in dopamine-producing neurons in the pars compacta of the dopamine-producing substantia nigra. While dopamine in the body provides benefits within certain limit values and no side effects are observed, dopamine levels above the upper limit may result in dyskinesia, and dopamine levels below the lower limit may result in the patient's movements not improving (also called off or closed period).

Parkinson's disease is a disease in which individual differences in patient-based treatment results are very common, despite all treatment options. Levodopa preparations given to patients show an effect in the form of improvement in symptoms for 3.5-4.5 hours. However, while this effect is shorter in advanced stages, the investigators see in our daily practice that it is longer lasting in newly diagnosed patients.

The aim of our study is to compare dopamine levels by giving levodopa benserazide and levodopa carbidopa entacapone in patients with early-stage unilateral involvement or unilateral findings with axial involvement (fits Hoehn Yahr stages 1 and 1.5). The drug containing levodopa benserazide (madopar 125 mg) contains 100 mg levodopa and 25 mg benserazide, which prevents the peripheral destruction of levodopa. The other drug, dopalevo, contains 100 mg levodopa, 25 mg carbidopa and 200 mg entacapone, which is a similar formulation to madopar. While entacapone reduces the daily off level by 0.6-0.9 hours, it also reduces the peripheral destruction of levodopa. Carbidopa and entacapone prevent the degradation of levodopa by different mechanisms. Namely, by inhibiting the dopa decarboxylase enzyme, benserazide contained in Madopar tablet reduces the conversion of levodopa into dopamine before it reaches the brain and increases the amount of dopamine reaching the brain. In Dopalevo, carbidopa, which is found next to levodopa, has a similar effect to benserazide by inhibiting the dopa decarboxylase enzyme, while the other molecule, entacapone, prevents the destruction of levodopa by two different mechanisms by inhibiting the catecholamine-O-methyl transferase enzyme. Despite their differences in clinical effects, side effects and composition, these two drugs are frequently used interchangeably. Since side effects may occur depending on the active molecule or excipients in the drug, patients will also be monitored for side effects that may occur within 3 hours. Since levodopa-containing drugs and dopamine agonists are the most commonly used drugs in treatment in our country, it is expected that many patients included in the study will also be using levodopa-containing drugs. The aim of the study is to obtain data about the peripheral elimination of levodopa and blood level changes by measuring peripheral dopamine blood levels between patients receiving benserazide as DDCI and patients receiving carbidopa+entacapone in patients receiving the same levodopa dose. In this way, it is aimed to gain information about the treatment choice between these two drugs.

Patients admitting to Neurologyclinic will be included in the study. After obtaining consent from the patients, in the clinical procedure room; Blood will be taken just before taking the medicine and at the 90th and 180th minutes after taking the medicine. Sociodemographic characteristics of the patient such as age and gender, body mass index, disease duration (in months), disease type (tremor dominant/akinetic rigid), whether the patient spent the last 10 years in urban or rural areas before the disease was diagnosed, whether there are side effects after taking medication, if any. At what minute it developed, the Parkinson's medications and dosages taken (levodopa preparations, MAO inhibitors, dopamine agonists) and the last medication hours will be recorded. Patients will be randomized with a random allocation program and the drug to be given will be decided.