Ropinirole
Descripción general
Descripción
Ropinirol es un agonista de la dopamina no ergolina que se utiliza principalmente en el tratamiento de la enfermedad de Parkinson y el síndrome de piernas inquietas. Fue aprobado por primera vez para uso médico en los Estados Unidos en 1997. Ropinirol funciona estimulando los receptores de dopamina D2 en el cerebro, lo que ayuda a aliviar los síntomas asociados con la deficiencia de dopamina .
Mecanismo De Acción
Ropinirol ejerce sus efectos estimulando selectivamente los receptores de dopamina D2 dentro del sistema caudado-putamen en el cerebro. Esta estimulación ayuda a compensar la deficiencia de dopamina observada en condiciones como la enfermedad de Parkinson. Ropinirol tiene una alta afinidad por los receptores D2 y D3, con una mayor afinidad por los receptores D3 .
Análisis Bioquímico
Biochemical Properties
Ropinirole plays a crucial role in biochemical reactions by acting as a dopamine receptor agonist. It specifically targets dopamine D2 and D3 receptors, with a higher affinity for D3 receptors . By binding to these receptors, this compound stimulates dopaminergic activity in the brain, which helps alleviate symptoms of Parkinson’s disease and Restless Legs Syndrome . The interaction with these receptors is essential for its therapeutic effects.
Cellular Effects
This compound influences various cellular processes, particularly in neurons. It enhances dopaminergic signaling, which is vital for motor control and coordination . This compound also affects gene expression by modulating the activity of dopamine receptors, leading to changes in cellular metabolism and function . Additionally, this compound has been shown to protect neurons from apoptosis and reduce inflammation in certain cellular models .
Molecular Mechanism
At the molecular level, this compound exerts its effects by binding to dopamine D2 and D3 receptors, which are G-protein-coupled receptors . This binding activates intracellular signaling pathways, including the inhibition of adenylate cyclase and the modulation of ion channels . These actions result in increased dopaminergic activity, which helps improve motor function and reduce symptoms of Parkinson’s disease and Restless Legs Syndrome .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound have been observed to change over time. Studies have shown that this compound is stable under standard conditions but can degrade under extreme conditions . Long-term exposure to this compound has been associated with sustained improvements in motor function and reduced “off-time” in patients with Parkinson’s disease . Prolonged use can also lead to tolerance and the need for higher doses to achieve the same therapeutic effects .
Dosage Effects in Animal Models
In animal models, the effects of this compound vary with different dosages. Low doses of this compound have been shown to improve motor function and reduce symptoms of Parkinson’s disease . High doses can lead to adverse effects such as dyskinesia and compulsive behaviors . Studies have also indicated a threshold effect, where doses above a certain level do not provide additional therapeutic benefits and may increase the risk of side effects .
Metabolic Pathways
This compound is metabolized primarily in the liver by the cytochrome P450 enzyme CYP1A2 . The major metabolic pathways include N-despropylation and hydroxylation, resulting in the formation of inactive metabolites . These metabolites are then excreted through the kidneys. The metabolism of this compound can be influenced by other drugs that affect CYP1A2 activity, leading to potential drug interactions .
Transport and Distribution
This compound is widely distributed throughout the body, with a volume of distribution of approximately 7.5 L/kg . It is about 40% bound to plasma proteins and has a blood-to-plasma ratio of 1:1 . The compound is rapidly absorbed and extensively distributed from the vascular compartment to various tissues . The transport and distribution of this compound are crucial for its therapeutic effects, as it needs to reach the brain to exert its dopaminergic activity .
Subcellular Localization
The subcellular localization of this compound is primarily within the cytoplasm and at the cell membrane, where it interacts with dopamine receptors . The compound’s localization is influenced by its lipophilicity and the presence of specific transporters that facilitate its entry into cells . This compound’s activity is dependent on its ability to reach and bind to dopamine receptors, which are predominantly located on the cell membrane .
Métodos De Preparación
Rutas sintéticas y condiciones de reacción
Ropinirol se puede sintetizar mediante varios métodos. Un método común implica la reducción de un precursor de ácido 2-nitrofenil acético seguido de una ciclización espontánea. Otro método implica la ciclización reductiva de 2-(2'-bromo-etil) β-nitroestireno usando paladio sobre carbón (Pd/C) como catalizador .
Métodos de producción industrial
En entornos industriales, el clorhidrato de ropinirol a menudo se prepara disolviendo el compuesto en solventes como etanol, metanol o acetato de etilo, seguido de la adición de Pd/C. Luego, la mezcla se hace reaccionar para obtener el producto deseado .
Análisis De Reacciones Químicas
Tipos de reacciones
Ropinirol experimenta varias reacciones químicas, que incluyen:
Oxidación: Ropinirol se puede oxidar para formar diferentes metabolitos.
Reducción: La reducción de los grupos nitro a aminas es un paso clave en su síntesis.
Sustitución: Las reacciones de halogenación y sulfonación también están involucradas en su síntesis.
Reactivos y condiciones comunes
Oxidación: Los agentes oxidantes comunes incluyen peróxido de hidrógeno y permanganato de potasio.
Reducción: Se utilizan catalizadores como paladio sobre carbón (Pd/C) para la ciclización reductiva.
Sustitución: Se utilizan reactivos como cloruro de p-metilbencensulfonilo y piridina en reacciones de sustitución.
Principales productos formados
Los principales productos formados a partir de estas reacciones incluyen varios intermediarios que eventualmente conducen a la formación de clorhidrato de ropinirol .
Aplicaciones Científicas De Investigación
Ropinirol tiene una amplia gama de aplicaciones de investigación científica:
Química: Se utiliza como compuesto modelo en estudios que involucran agonistas de la dopamina.
Biología: Ropinirol se utiliza para estudiar los efectos de los agonistas de la dopamina en las vías celulares.
Medicina: Se utiliza ampliamente en el tratamiento de la enfermedad de Parkinson y el síndrome de piernas inquietas.
Comparación Con Compuestos Similares
Compuestos similares
Pramipexol: Otro agonista de la dopamina no ergolina que se utiliza en el tratamiento de la enfermedad de Parkinson y el síndrome de piernas inquietas.
Singularidad
Ropinirol es único por su alta afinidad por los receptores D3 en comparación con otros agonistas de la dopamina. Esta especificidad puede contribuir a su eficacia en el tratamiento de los síntomas de la enfermedad de Parkinson y el síndrome de piernas inquietas .
Propiedades
IUPAC Name |
4-[2-(dipropylamino)ethyl]-1,3-dihydroindol-2-one |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C16H24N2O/c1-3-9-18(10-4-2)11-8-13-6-5-7-15-14(13)12-16(19)17-15/h5-7H,3-4,8-12H2,1-2H3,(H,17,19) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
UHSKFQJFRQCDBE-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCCN(CCC)CCC1=C2CC(=O)NC2=CC=C1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C16H24N2O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
91374-20-8 (hydrochloride) |
Source
|
| Record name | Ropinirole [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0091374219 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
DSSTOX Substance ID |
DTXSID8045195 |
Source
|
| Record name | Ropinirole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8045195 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
260.37 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Ropinirole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014413 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Boiling Point |
410.5±45.0 °C at 760 mmHg |
Source
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| Record name | Ropinirole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00268 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
Solubility |
3.53e-01 g/L |
Source
|
| Record name | Ropinirole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00268 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Ropinirole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014413 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Mechanism of Action |
Ropinirole is a non-ergoline dopamine agonist. Ropinirole has the highest affinity at the D3 receptors, which are concentrated in the limbic areas of the brain and may be responsible for some of the neuropsychiatric effects. The exact mechanism of action of ropinirole as a treatment for Parkinson’s disease is unknown, however, it is believed to be related to its ability to selectively stimulate dopamine D2 receptors within the caudate-putamen system in the brain. This system affects body movement. Negligible affinity is seen for ropinirole at α2 adrenoreceptors in the periphery and 5HT-1 receptor. Ropinirole has no affinity at the D1-like receptors, benzodiazepine or GABA receptors. The precise mechanism of action of ropinirole as a treatment for Restless Legs Syndrome is unknown, however, it is believed to be related to its ability to stimulate dopamine receptors., The present study determined its affinity and agonist efficacy at recombinant human (h) dopamine hD2, hD3 and hD4 and serotonin (5-HT) h5-HT1A, h5-HT1B and h5-HT1D receptors. Roxindole exhibited high affinity at hD3 as well as at hD2 (short isoform) and hD4 (4-repeat isoform) receptors (pKi values 8.93, 8.55 and 8.23, respectively). Further, it displayed high affinity at hS-HT1A receptors (pKi = 9.42) but modest affinity at 5-HT1B and 5-HT1D receptors (pKi values 6.00 and 7.05, respectively). In [35S]GTPgammaS binding experiments, roxindole was >20-fold more potent in stimulating [35S]GTPgammaS binding at hD3 than at hD2 or hD4 receptors (pEC50 = 9.23 vs. 7.88 and 7.69). However, whereas roxindole exhibited partial agonist activity at hD3 and hD4 sites (Emax = 30.0% and 35.1%, respectively, relative to dopamine = 100%), it only weakly activated hD2 receptors (Emax = 10.5%). Roxindole potently blocked dopamine-stimulated [35S]GTPgammaS binding at hD2 receptors (pkappaB = 9.05). In comparison, the dopamine receptor agonist, (-)quinpirole, acted as a partial agonist at hD3 and hD4 sites (Emax = 67.4% and 66.3%, respectively) but surpassed the efficacy of dopamine at hD2 receptors (Emax = 132%). At h5-HT1A receptors, roxindole behaved as a high affinity (pKi = 9.42) partial agonist (Emax = 59.6%, relative to 5-HT = 100%), whereas (-)quinpirole had negligible activity. The selective 5-HT1A antagonist, WAY 100,635, blocked roxindole (100 nM)-stimulated [35S]GTPgammaS binding at h5-HT1A receptors in a concentration-dependent manner (pkappaB = 9.28). Roxindole only weakly stimulated [35S]GTPgammaS binding at 5-HT1B and 5-HT1D receptors (Emax = 27.1% and 13.7%). The present data suggest that roxindole activates mainly D3 vs. D2 or D4 receptors and 5-HT1A vs. 5-HT1B or 5-HT1D receptors. Activation of D3 and/or 5-HT1A receptors may thus contribute to its potential antidepressant properties., The aim of the present study was to characterize functional responses to ropinirole, its major metabolites in man (SKF-104557 (4-[2-(propylamino)ethyl]-2-(3H) indolone), SKF-97930 (4-carboxy-2-(3H) indolone)) and other dopamine receptor agonists at human dopamine D2(long) (hD2), D3 (hD3) and D4.4 (hD4) receptors separately expressed in Chinese hamster ovary cells using microphysiometry. 2. All the receptor agonists tested (ropinirole, SKF-104557, SKF-97930, bromocriptine, lisuride, pergolide, pramipexole, talipexole, dopamine) increased extracellular acidification rate in Chinese hamster ovary clones expressing the human D2, D3 or D4 receptor. The pEC50s of ropinirole at hD2, hD3 and hD4 receptors were 7.4, 8.4 and 6.8, respectively. Ropinirole is therefore at least 10 fold selective for the human dopamine D3 receptor over the other D2 receptor family members. 3. At the hD2 and hD3 dopamine receptors all the compounds tested were full agonists as compared to quinpirole. Talipexole and the ropinirole metabolite, SKF-104557, were partial agonists at the hD4 receptor. 4. Bromocriptine and lisuride had a slow onset of agonist action which precluded determination of EC50s. 5. The rank order of agonist potencies was dissimilar to the rank order of radioligand binding affinities at each of the dopamine receptor subtypes. Functional selectivities of the dopamine receptor agonists, as measured in the microphysiometer, were less than radioligand binding selectivities. 6. The results show that ropinirole is a full agonist at human D2, D3 and D4 dopamine receptors. SKF-104557 the major human metabolite of ropinirole, had similar radioligand binding affinities to, but lower functional potencies than, the parent compound., Ropinirole, which is a non-ergot dopamine agonist derivative, exerts therapeutic benefits in Parkinson's disease (PD). Based on recent studies implicating dopamine receptors 2 and 3 (D2R and D3R) as possible targets of ropinirole, we over-expressed these dopamine receptor genes in the dopamine-denervated striatum of rodents to reveal whether their over-expression modulated ropinirole activity. Adult Sprague-Dawley rats initially received unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At 1 month after surgery, successfully lesioned animals (3 or less forelimb akinesia score, and 8 or more apomorphine-induced rotations/min over 1 hr) were randomly assigned to intrastriatal injection (ipsilateral to the lesion) of blank lentiviral vector, D2R, D3R or both genes. At about 5 months post-lesion, ropinirole (0.2 mg/kg, i.p.) was administered daily for 9 consecutive days. The subtherapeutic dose of ropinirole improved the use of previously akinetic forelimb and produced robust circling behavior in lesioned animals with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. In contrast, the subtherapeutic dose of ropinirole generated only modest motor effects in lesioned animals with sole over-expression of D2R or D3R. Western immunoblot and autoradiographic assays showed enhanced D2R and D3R protein levels coupled with normalized D2R and D3R binding in the ventral striatum of lesioned animals with lentiviral over-expression of both D2R and D3R relative to vehicle-treated lesioned animals. Immunohistochemical analyses showed that D2R and D3R GFP fluorescent cells colocalized with enkephalin and substance P immunoreactive medium spiny neurons. These data support the use of the subtherapeutic dose of ropinirole in a chronic model of PD., Ropinirole hydrochloride, a dipropylaminoethyl indolone derivative, is a nonergot-derivative dopamine receptor agonist. In in vitro binding studies, ropinirole demonstrated high binding specificity for and intrinsic activity at dopamine D2 receptors compared with other dopamine receptor agonists (e.g., bromocriptine, pergolide), having a higher affinity for the D3 subtype than for the D2 or D4 subtypes. Ropinirole binds with moderate affinity to opiate receptors but has little or no affinity for alpha1-, alpha2-, or beta-adrenergic; dopamine D1; benzodiazepine; gamma-aminobutyric acid (GABA); serotonin type 1 (5-hydroxytryptamine (5-HT1)); serotonin type 2 (5-HT2); or muscarinic receptors. |
Source
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| Record name | Ropinirole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00268 | |
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| Record name | ROPINIROLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/8252 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
CAS No. |
91374-21-9 |
Source
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| Record name | Ropinirole | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=91374-21-9 | |
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| Record name | Ropinirole [USAN:INN:BAN] | |
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| Record name | Ropinirole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00268 | |
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| Record name | ropinirole | |
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| Record name | 2H-Indol-2-one, 4-[2-(dipropylamino)ethyl]-1,3-dihydro | |
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| Record name | Ropinirole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014413 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
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Melting Point |
243-250 °C, 243 - 250 °C |
Source
|
| Record name | Ropinirole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00268 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Ropinirole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014413 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
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Retrosynthesis Analysis
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| Precursor scoring | Relevance Heuristic |
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| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
Q1: How does ropinirole interact with its target?
A: this compound is a non-ergoline dopamine agonist that primarily targets dopamine D2-like receptors, exhibiting a high affinity for both D2 and D3 subtypes. [, , , ] It mimics the action of dopamine by binding to these receptors, leading to downstream signaling events.
Q2: What are the downstream effects of this compound binding to dopamine receptors?
A: The binding of this compound to D2-like receptors, particularly in the striatum, helps restore dopaminergic signaling, which is deficient in Parkinson’s disease. [, , ] This, in turn, helps alleviate motor symptoms such as tremors, rigidity, and bradykinesia.
Q3: What is the molecular formula and weight of this compound?
A3: this compound has the molecular formula C16H24N2O2 and a molecular weight of 276.37 g/mol.
Q4: Is there any spectroscopic data available for this compound?
A: While the provided research articles do not delve into detailed spectroscopic data, studies often employ techniques like UV spectrophotometry and RP-HPLC for this compound analysis. []
Q5: What are the different formulations of this compound available?
A: this compound is available in both immediate-release and 24-hour prolonged-release formulations. [, , , , , ] The prolonged-release formulation aims to maintain more consistent dopaminergic activity with steadier plasma levels, potentially leading to improved tolerability and compliance.
Q6: How is this compound absorbed and distributed in the body?
A: this compound is rapidly and almost completely absorbed after oral administration. [, , ] It exhibits good distribution throughout the body, crossing the blood-brain barrier to reach its target sites in the brain. []
Q7: What is the primary route of this compound metabolism?
A: this compound is extensively metabolized in the liver, primarily by the cytochrome P450 (CYP) isoenzyme CYP1A2. [, , ] It also undergoes metabolism by CYP3A4/5 to a lesser extent. []
Q8: How is this compound eliminated from the body?
A: The primary route of this compound elimination is renal excretion, with approximately 60-90% of the administered dose being eliminated through urine. []
Q9: Does the presence of other drugs affect this compound pharmacokinetics?
A: Co-administration with drugs that are CYP1A2 inhibitors, such as ciprofloxacin, can significantly increase the systemic availability of this compound. [] On the other hand, co-administration with theophylline, a CYP1A2 substrate, did not significantly alter this compound pharmacokinetics. []
Q10: Does the use of estrogen replacement therapy affect this compound pharmacokinetics in women?
A: Yes, in women receiving long-term estrogen replacement therapy, oral clearance of this compound is reduced, and its elimination half-life is prolonged. [] Dosage adjustments may be necessary when starting or stopping estrogen replacement therapy during this compound treatment.
Q11: What preclinical models have been used to study the effects of this compound?
A: Preclinical studies have utilized various animal models, including rats with unilateral 6-hydroxydopamine lesions, to investigate the effects of this compound on motor symptoms, dyskinesia, and gliovascular changes associated with Parkinson's disease. []
Q12: What clinical trials have been conducted on this compound?
A: Numerous clinical trials have investigated the efficacy and safety of this compound in treating Parkinson's disease and restless legs syndrome (RLS). These trials include randomized, double-blind, placebo-controlled studies, crossover studies, and long-term efficacy studies. [, , , , , , , , , ]
Q13: Has this compound demonstrated efficacy in treating restless legs syndrome (RLS)?
A: Yes, clinical trials have demonstrated that this compound effectively reduces RLS symptoms, including the urge to move legs, uncomfortable sensations, and sleep disturbances. [, , , ]
Q14: What is the efficacy of this compound compared to other dopamine agonists in treating Parkinson's disease?
A: Clinical trials have compared this compound with other dopamine agonists like bromocriptine and pramipexole. [, , ] Results suggest that this compound exhibits comparable efficacy in improving motor symptoms, but individual patient responses may vary.
Q15: Are there any known mechanisms of resistance to this compound?
A: While this compound resistance is not extensively discussed in the provided articles, long-term use of dopamine agonists, in general, can lead to a decline in efficacy and the development of motor complications. [, , ] The exact mechanisms underlying this resistance are complex and require further investigation.
Q16: Does this compound induce or inhibit drug-metabolizing enzymes?
A: While the provided articles do not extensively discuss enzyme induction or inhibition by this compound, its metabolism by CYP1A2 suggests the potential for drug interactions. [, ] Co-administration with CYP1A2 inhibitors or inducers may necessitate dosage adjustments.
Q17: What are the alternative treatments for Parkinson's disease and RLS?
A: Alternative treatments for Parkinson's disease include levodopa (often considered the gold standard), other dopamine agonists (e.g., pramipexole, rotigotine), MAO-B inhibitors (e.g., selegiline, rasagiline), and COMT inhibitors (e.g., entacapone). [, , , , , , ] For RLS, alternatives include gabapentin, opioids, benzodiazepines, and iron supplementation. []
Q18: When was this compound first introduced as a treatment for Parkinson’s disease?
A: this compound received approval for the treatment of Parkinson’s disease in the late 1990s. [, ]
Q19: Can this compound be used as monotherapy in early Parkinson’s disease?
A: Yes, this compound is approved for use as both early monotherapy and as an adjunct to levodopa in the treatment of Parkinson's disease. [, , , , ]
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