Pramipexole

Parkinson's Disease

This compound is indicated for the symptomatic treatment of idiopathic Parkinson's Disease, and its efficacy has been evaluated in both early and advanced stages of the disease. probes-drugs.org

In patients with early Parkinson's Disease who are not receiving levodopa therapy, clinical trials have shown this compound to be effective as monotherapy. A multicenter, randomized, double-blind trial involving 335 patients with early PD demonstrated that this compound significantly reduced the severity of symptoms and signs compared with placebo. neurology.orgnih.gov Improvements were measured by decreases in parts II (Activities of Daily Living) and III (Motor Examination) of the Unified Parkinson's Disease Rating Scale (UPDRS) at week 24 compared to baseline. neurology.orgnih.gov Significant differences between the this compound and placebo groups emerged as early as week 3 and persisted throughout the 24-week maintenance phase. neurology.orgnih.gov Another study in 264 patients with early PD showed a approximately 20% improvement in total UPDRS scores after 10 weeks of treatment with this compound across various dosages compared to placebo. jwatch.orgnih.gov

For patients with advanced Parkinson's Disease experiencing motor fluctuations while on levodopa therapy, this compound has proven effective as adjunctive treatment. Double-blind, placebo-controlled studies have shown that adding this compound to individually adjusted levodopa therapy improves UPDRS sum scores of parts II and III and reduces "off" times. researchgate.netnih.gov One study in 354 patients with motor fluctuations demonstrated a 30% improvement in UPDRS sum scores and a reduction in off times by approximately 2.5 hours per day with this compound treatment. researchgate.netnih.gov Differences in efficacy compared to placebo became significant at a daily dose of 0.75 mg of this compound dihydrochloride. nih.gov Studies have also indicated that this compound as an adjunct to levodopa can lead to a reduction in daily levodopa usage. nih.govmedcentral.comnih.gov A network meta-analysis concluded that the addition of this compound to levodopa treatment in advanced PD patients with motor fluctuations can increase "ON" time without troublesome dyskinesia and improve UPDRS Part II and Part III scores. frontiersin.org

Clinical research consistently shows that this compound has a positive impact on key motor symptoms of Parkinson's Disease, as measured by the UPDRS and reductions in "off" time. In monotherapy for early PD, this compound significantly improves UPDRS Parts II and III scores. neurology.orgnih.gov As adjunctive therapy in advanced PD, it leads to improvements in UPDRS Parts II and III scores and a significant reduction in the duration of daily "off" time. researchgate.netnih.govnih.govmedcentral.comnih.gov Patients with pronounced resting tremor may derive a clear benefit from this compound treatment compared with placebo. researchgate.netnih.gov One study noted a greater antitremor effect for this compound compared to placebo based on UPDRS tremor-related items. nih.gov

Here is a summary of key efficacy findings in Parkinson's Disease:

While the prompt requests exclusion of tolerability, studies have assessed the long-term efficacy of this compound in Parkinson's Disease. An open-label extension study following a double-blind trial in patients with advanced PD and motor fluctuations assessed long-term efficacy for up to 57 months. researchgate.netnih.gov Statistical analysis revealed good long-term efficacy of this compound. researchgate.netnih.gov Another open-label study assessing long-term efficacy over a four-year period in patients with moderate to severe PD experiencing motor fluctuations found that this compound treatment appeared to show continued efficacy for 3 years, with a gradual return to baseline motor states observed after 3 years, potentially suggesting disease progression. nih.gov UPDRS Part IV scores remained below baseline for the duration of this study, indicating an improvement. nih.gov Tremor during "on" periods also showed improvement over baseline for the study duration. nih.gov

Impact on Motor Symptoms (e.g., UPDRS scores, OFF-time, tremor)

Restless Legs Syndrome

This compound is also indicated for the symptomatic treatment of moderate to severe primary Restless Legs Syndrome (RLS). probes-drugs.org Clinical trials have demonstrated its efficacy in reducing RLS symptoms. A 12-week, double-blind, randomized, placebo-controlled trial in patients with moderate to severe RLS showed that this compound was superior to placebo in reducing symptom severity, as measured by the International RLS Study Group Rating Scale (IRLS). neurology.org this compound also increased the percentage of patients with a Clinical Global Impressions-Improvement (CGI-I) rating of "very much improved" or "much improved". neurology.org Significant treatment effects were observed on secondary efficacy endpoints, including quality of life ratings and visual analogue scale ratings related to sleep satisfaction and symptom severity. neurology.org this compound significantly improved patient ratings on all sleep-related measures, including symptom severity while getting to sleep, during the night, and during the day. neurology.org A meta-analysis of randomized controlled trials indicated that this compound could effectively improve the symptoms of patients with primary moderate-to-severe RLS. researchgate.net Another study comparing this compound with dual-release levodopa in de novo RLS patients found both treatments effective in reducing periodic limb movements (PLM index) and RLS symptoms (IRLS score), with comparable effects in short-term treatment of mild to moderate RLS. smw.ch In patients with more severe RLS (IRLS score >20), a significantly higher PLMI reduction was found with this compound compared to levodopa. smw.ch this compound has also been shown to effectively suppress PLM, which are often associated with RLS. researchgate.net

Here is a summary of key efficacy findings in Restless Legs Syndrome:

Short-term Efficacy Studies (e.g., RLSRS, CGI-I scores)

Short-term clinical trials have investigated the efficacy of this compound in patients with moderate to severe idiopathic Restless Legs Syndrome (RLS). Studies ranging from 3 to 12 weeks in duration have utilized standardized rating scales such as the International Restless Legs Syndrome Rating Scale (IRLSRS or RLSRS) and the Clinical Global Impression-Improvement (CGI-I) scale to assess treatment outcomes.

A 3-week, double-blind, placebo-controlled, dose-finding study evaluated the effects of this compound across doses of 0.125 mg/d to 0.75 mg/d in patients with moderate to severe RLS. This study demonstrated that all tested doses of this compound significantly decreased the periodic limb movements during time in bed index (PLMI) compared to placebo. researchgate.net Furthermore, significant reductions in IRLS scores were observed across all this compound dose groups, with the greatest adjusted mean reduction noted in the 0.50 mg group. researchgate.net The percentage of patients achieving at least a 50% reduction in IRLS score was substantially higher in the this compound groups (ranging from 61.9% to 77.3%) compared to the placebo group (33.3%). researchgate.net On the CGI-I scale, a significantly higher percentage of patients in the this compound groups (61.9% to 86.4%) were rated as 'much improved' or 'very much improved' compared to the placebo group (42.9%). researchgate.net

Another short-term study, lasting 6 weeks, also used the change in RLSRS total score from baseline and the proportion of CGI-I responders as primary endpoints, observing a significant response for both with this compound treatment. europa.eu A 12-week fixed-dose study similarly employed RLSRS and CGI-I as primary endpoints to evaluate this compound's efficacy. europa.eu

A meta-analysis of randomized clinical trials with an average treatment duration of 11.12 weeks further supported the short-term efficacy of this compound in RLS. This analysis showed a significantly superior reduction in IRLS scores in the this compound group compared to placebo. nih.gov The meta-analysis also indicated that the proportion of responders based on IRLS, CGI-I, and Patient Global Impression (PGI) scales was significantly higher with this compound treatment. nih.gov

The findings from these short-term studies indicate that this compound is effective in reducing RLS symptom severity and improving patients' global impression of their condition within weeks of initiating treatment.

Long-term Efficacy and Augmentation Phenomena

While effective in the short term, the long-term use of dopaminergic agonists like this compound in RLS is associated with the phenomenon of augmentation. Augmentation is characterized by a worsening of RLS symptoms, typically occurring earlier in the day, increasing in intensity, and potentially spreading to other body parts. researchgate.netfrontiersin.org

Long-term studies have provided insights into the sustained efficacy and the incidence of augmentation with this compound. A cohort study following 50 patients treated with this compound for a mean duration of 8 years (range 0.6-12 years) reported that while the majority of patients remained on the drug, its complete effectiveness decreased over time. researchgate.netnih.gov At the end of the study, 40% of patients reported complete effectiveness, compared to 67% at the end of the initial study period. researchgate.netnih.gov Augmentation developed in 42% of patients, with a mean time to onset of 16.5 months, and occurring no later than 4.1 years after starting treatment. researchgate.netnih.gov

A retrospective assessment of 59 patients treated with this compound for at least 6 months (mean duration 21.2 months) found that augmentation developed in 32% of patients at a mean duration of 8.5 months. Tolerance, defined as the need for a dose increase to maintain the original effect, occurred in 46% of these patients.

Research suggests that the rate of augmentation increases with the duration of dopaminergic treatment. Short-term studies report augmentation rates around 10%, while studies lasting 2-3 years show rates of 15-30%, and those extending to around 10 years report rates between 42% and 68%. frontiersin.org The development of augmentation within the first four years of therapy is highlighted as a significant issue with long-term this compound use. researchgate.netnih.gov

While some studies with open-label extensions have shown maintained reductions in RLSRS scores over periods like 6 months, the interpretation of sustained efficacy in long-term trials can be complex due to study design and the potential for confounding factors like rebound effects upon withdrawal. europa.eu The consistent observation of a reduction in efficacy with increased trial duration across studies underscores the challenge of maintaining long-term effectiveness and the associated risk of augmentation. europa.eunih.gov

The data suggest that while this compound provides significant relief in the short term for RLS, the potential for developing augmentation and a decrease in complete efficacy over extended treatment periods are important considerations in its long-term management.

Effects on Periodic Limb Movements and Sleep Parameters

This compound has been shown to have a significant impact on periodic limb movements (PLM) and various sleep parameters in patients with RLS. PLM are involuntary, repetitive movements of the limbs that often occur during sleep and wakefulness, contributing to sleep disturbance in RLS.

In a 3-week dose-finding study, this compound significantly reduced the periodic limb movements during time in bed index (PLMI) across all tested doses (0.125 mg/d to 0.75 mg/d) compared to placebo. researchgate.netnih.gov After 3 weeks of treatment, all this compound doses reduced the median PLM while asleep to levels generally considered normal (<5 PLM/h). nih.gov

Beyond reducing the frequency of PLM, this compound also demonstrated effects on sleep architecture. The 3-week study indicated that median sleep latency was reduced in the this compound groups compared to placebo. nih.gov Median total sleep time increased, reaching statistical significance in the 0.50 mg/d group. nih.gov Similarly, the median time spent in stages 2-4/REM sleep increased, also significantly in the 0.50 mg/d group. nih.gov Subjective ratings of sleep disturbance reported by patients were also significantly improved with this compound treatment. nih.gov

A study investigating the effects of a single dose of 0.25 mg this compound demonstrated a significant reduction in the periodic limb movement during sleep (PLMS) index and an increase in sleep efficiency compared to placebo. oup.com This study also found that PLMS while asleep and awake were significantly lower in the this compound group. oup.com Interestingly, the mean duration of PLMS was slightly but significantly increased with this compound. oup.com The percentage of sleep stage 2 also increased after a single dose. oup.com

Collectively, these findings indicate that this compound is effective in objectively reducing periodic limb movements and subjectively improving sleep quality in patients with RLS. The effects on sleep parameters include reductions in sleep latency and increases in total sleep time and certain sleep stages.

Depressive Disorders

This compound has been investigated as a potential treatment for various depressive disorders, including bipolar depression, unipolar depression, treatment-resistant depression, and anhedonic depression. Its mechanism of action as a dopamine agonist, particularly with high affinity for the D3 receptor, provides a rationale for its use in conditions potentially associated with dopaminergic dysfunction. bmj.combmj.comnih.gov

Evidence suggests potential efficacy in treatment-resistant depression, encompassing both unipolar and bipolar forms. nih.govnih.govpsychiatryonline.org A systematic review and meta-analysis of observational studies on this compound augmentation in treatment-resistant unipolar and bipolar depression reported a pooled estimate of treatment response of 62.5%. nih.gov The response rates were similar between unipolar (56.7%) and bipolar (66.0%) depression in this analysis. nih.gov Another meta-analysis mentioned a 52.2% response rate in the short term and 62.1% in the long term for this compound treatment in mood disorders, with corresponding remission rates of 36.1% and 39.6%. nih.gov

A case series involving adjunctive this compound in patients with treatment-resistant depression who had failed multiple previous treatments showed a meaningful clinical response in 76% of patients. psychiatryonline.org However, a randomized controlled trial comparing adjunctive this compound to placebo in outpatients with major depression who had not responded to at least one antidepressant found only a modest statistically significant benefit for this compound, with no significant differences in response or remission rates between the groups. psychiatryonline.org

This compound is also being specifically investigated for anhedonic depression, a subtype characterized by a reduced ability to experience pleasure and lack of motivation, symptoms potentially linked to dopaminergic hypofunction. bmj.combmj.comoup.com An open-label pilot study in patients with unipolar or bipolar moderate to severe depression and significant anhedonia demonstrated significant improvement in anhedonia and depression scores over 10 weeks of adjunctive this compound treatment. oup.com These preliminary findings suggest potential efficacy in this specific depressive subtype, but further research, including randomized controlled trials, is needed. bmj.combmj.comoup.comclinicaltrials.eu

While research indicates promising results, particularly in treatment-resistant and anhedonic depression, further large-scale, controlled studies are necessary to establish the definitive role of this compound in the treatment of depressive disorders.

Essential Tremors

The potential efficacy of this compound in essential tremor (ET) has been explored in clinical research, although the evidence is currently limited. Essential tremor is a neurological disorder characterized by involuntary shaking, often in the hands and arms.

While this pilot study suggests that this compound may hold promise for the treatment of essential tremor, the authors emphasize the need for further controlled studies to confirm these findings. nih.govresearchgate.net An evidence-based medicine guideline indicates that there is currently insufficient evidence to either recommend or advise against the use of this compound in patients with essential tremor. tandfonline.com Clinical experience with this compound in ET remains limited, and the existing evidence primarily stems from this pilot study. tandfonline.com Preclinical studies in animal models of essential tremor have shown that low-dose this compound can reduce tremor, potentially associated with changes in gene expression in brain areas involved in tremor generation. tandfonline.com

Chronic Pain Conditions

The potential analgesic effects of this compound have been investigated in various chronic pain conditions, including opioid-induced tolerance and nociceptive pain. The involvement of dopaminergic pathways in pain modulation provides a rationale for exploring dopamine agonists in pain management.

Preclinical studies in animal models have suggested that this compound may play a role in modulating pain. In rats experiencing chronic inflammatory pain, both acute and repeated treatment with this compound attenuated mechanical hypersensitivity, whereas it had no such effect in control animals. iasp-pain.orgnih.gov These findings suggest that alterations in dopamine D2/3 receptor signaling, which are influenced by this compound, may be associated with anti-hyperalgesic effects in the context of chronic pain. iasp-pain.org

Clinical observations and studies have also explored this compound's effects on pain in humans. This compound has been reported to show efficacy on pain associated with Parkinson's disease. mdpi.comconicet.gov.ar In a case report, this compound was used effectively to treat a patient with burning mouth syndrome. mdpi.comconicet.gov.ar A study in patients with fibromyalgia, a chronic condition characterized by widespread pain, found that this compound decreased visual analog scale (VAS) scores for pain significantly compared to placebo. mdpi.comconicet.gov.ar However, pain was a secondary outcome in this trial, and patients were not specifically selected based on their pain severity, which might influence the interpretation of these results. mdpi.comconicet.gov.ar Another study in fibromyalgia where chronic this compound provided some pain relief noted that over half of the patients were also taking a narcotic, potentially suggesting a synergistic effect. nih.gov

Furthermore, this compound has been investigated for its ability to enhance opioid-mediated analgesia and potentially mitigate opioid-induced tolerance. A recent study suggested that this compound could effectively reduce tolerance to morphine and shorten the duration of withdrawal symptoms in chronically treated patients. nih.gov A pilot clinical trial in patients with acute renal colic demonstrated that adjunctive treatment with this compound and a half-dose of morphine achieved effective analgesia in a significantly higher percentage of patients compared to treatment with a standard dose of morphine and placebo. nih.gov This suggests that this compound may enhance the analgesic effects of opioids, potentially allowing for lower opioid doses and reduced associated risks. nih.gov Preclinical studies have also shown that this compound can enhance morphine's analgesic effects in animal models of acute and chronic pain. nih.gov

The research to date suggests that this compound may have analgesic properties and the potential to augment opioid effects in certain pain conditions. However, more extensive and controlled clinical trials are needed to fully understand its efficacy and role in the management of various chronic pain states and opioid-related issues.

REM Sleep Behavior Disorder

Research has investigated the efficacy of this compound in treating Rapid Eye Movement (REM) sleep behavior disorder (RBD), a parasomnia characterized by REM sleep without atonia and motor activity associated with dreaming. nih.govjst.go.jp Studies suggest a potential involvement of dopaminergic dysfunction in the pathophysiology of RBD, given its association with Parkinson syndromes and restless legs syndrome. worldsleepsociety.orgnih.gov

In a case series involving patients with polysomnographically confirmed RBD, treatment with this compound resulted in a marked reduction in the frequency and severity of RBD symptoms. worldsleepsociety.orgnih.gov Specifically, 89% of patients in this series experienced either a moderate reduction or complete resolution in the frequency of their RBD symptoms, and 67% reported at least a moderate reduction in symptom intensity. worldsleepsociety.orgnih.gov This symptomatic improvement appeared to be maintained over a follow-up period of up to 25 months. worldsleepsociety.orgnih.gov

Another study involving patients with RBD and a high periodic leg movement during sleep (PLMS) index also evaluated this compound's effectiveness. nih.govjst.go.jp Fourteen out of fifteen patients (80.0%) showed symptomatic improvement of RBD with this compound treatment. nih.govjst.go.jp this compound treatment was associated with a reduction in REM density and the PLM index during non-REM sleep, although the amount of REM sleep without atonia remained unchanged. nih.govjst.go.jp The degree of change in RBD symptoms positively correlated with the reduction in REM density. nih.govjst.go.jp While this compound showed promise in reducing RBD symptoms, some research indicates it may not affect REM sleep characteristics except for a possible increase in muscle tone during REM sleep. neurology.org Further placebo-controlled studies with larger patient populations are needed to fully document the effect of this compound on RBD. neurology.org

Cerebral Ischemia and Reperfusion Injury Research

This compound has been explored for its potential neuroprotective effects in the context of cerebral ischemia and reperfusion injury. Studies in animal models have investigated its impact on neurological function and cellular damage following such events. biologists.comnih.govnih.gov

Research in rats subjected to global cerebral ischemia/reperfusion injury demonstrated that this compound treatment improved neurological behaviors and increased the number of surviving neurons in the hippocampal CA1 region. nih.govnih.gov this compound was found to restore mitochondrial ultrastructure, decrease tissue iron and malondialdehyde (MDA) concentrations, and increase glutathione (GSH) concentration in the brain of injured rats. nih.gov These findings suggest that this compound may exert neuroprotection by inhibiting ferroptosis, a form of cell death linked to iron and oxidative stress, through the Nrf2/GPX4/SLC7A11 pathway. nih.govconsensus.app

Different doses of this compound have been evaluated for their effects on neurological function and mitochondrial membrane potential in rats with global cerebral ischemia-reperfusion injury. nih.gov While multiple doses showed some degree of improvement, a dose of 0.5 mg/kg appeared to be particularly effective in consistently reducing modified neurological severity scores and improving neurological function. nih.gov This dose also significantly increased the mitochondrial membrane potential in rats after injury. nih.gov

Post-stroke treatment with this compound in ischemic stroke models has shown a reduction in infarction volume and improved neurological recovery. biologists.com this compound treatment reduced levels of mitochondrial reactive oxygen species (ROS) and Ca2+, elevated mitochondrial membrane potential, and increased mitochondrial oxidative phosphorylation. biologists.com It also inhibited the transfer of cytochrome c from mitochondria to the cytosol, suggesting an inhibition of the mitochondrial permeability transition pore. biologists.com These results indicate that this compound may induce neurological recovery through mitochondrial pathways in ischemia/reperfusion injury. biologists.com

Traumatic Brain Injury Research

The neuroprotective potential of this compound has also been investigated in the context of traumatic brain injury (TBI). Preclinical studies in animal models have explored its effects on behavioral deficits, oxidative stress, mitochondrial dysfunction, and blood-brain barrier integrity following TBI. nih.govbiologists.comnih.govresearchgate.netresearchgate.net

In rat models of TBI, this compound treatment has been shown to improve behavioral deficits, decrease lipid peroxidation rate, increase glutathione levels, and decrease levels of 4-hydroxynonenal. nih.govbiologists.com this compound also increased the activities of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase. nih.govbiologists.com Furthermore, this compound treatment inhibited mitochondrial ROS production, restored mitochondrial membrane potential, and increased ATP levels after TBI. nih.govbiologists.com It also influenced apoptotic pathways by reducing the Bax/Bcl2 ratio and translocation of Bax to mitochondria and cytochrome-c to the cytosol. nih.govbiologists.com These neuroprotective effects appear to be mediated, at least in part, by the activation of the Nrf2/HO-1 signaling pathway. nih.govbiologists.com

Research has also indicated that this compound may protect against TBI-induced blood-brain barrier (BBB) dysfunction. nih.govresearchgate.net In mice models of TBI, this compound treatment reversed neurofunctional deficits, behavioral disability, and aggravated pathological changes. nih.gov This was accompanied by alleviated BBB permeability and upregulated occludin, a key tight junction protein. nih.gov In vitro studies using TBI model cells further supported these findings, showing that this compound reversed increased endothelial permeability and downregulated occludin and KLF2 expression. nih.gov These results suggest that this compound's protective effect against TBI-induced BBB dysfunction may be mediated by KLF2. nih.gov

Additionally, studies have explored the mechanism of this compound's protective role after TBI through the inhibition of necroptosis, a mode of cell death. researchgate.net Observations in rat models suggest that this compound could improve the prognosis of TBI by inhibiting necroptosis and influencing the expression of receptor interacting protein 1 (RIP1) and its related proteins. researchgate.net

Binge Eating Disorder

This compound has been investigated for its potential in treating binge eating disorder (BED). clinicaltrials.eu While some clinical trials have explored this application, some Phase 3 trials for BED treatment with this compound have been withdrawn. drugbank.com

Case reports have described the development of compulsive eating behaviors in patients using dopamine agonists, including this compound, for other conditions such as Parkinson's disease. nih.govresearchgate.netpsychiatrist.com These reports suggest a potential association between this compound use and the onset of compulsive eating, sometimes resulting in significant weight gain. nih.govresearchgate.net In some cases, lowering the dose or discontinuing the dopamine agonist led to the remission of the compulsive eating behavior and cessation of further weight gain. nih.govresearchgate.net The association between dopaminergic activity in the mesolimbic pathway and compulsive behaviors, including compulsive eating, has been noted. psychiatrist.com Further investigation into this relationship is warranted. nih.govresearchgate.net

Age-related Macular Degeneration Research

Research has explored the potential of this compound as a therapeutic agent for age-related macular degeneration (AMD), a leading cause of irreversible visual impairment in older adults. nii.ac.jpnih.govarvojournals.orggoogle.com AMD exists in two major subtypes: dry (atrophic) and wet (neovascular). nii.ac.jp

Studies have investigated this compound's effects in animal models of AMD. In mice models of light-induced retinal damage, a model for dry AMD, both oral administration and ocular instillation of this compound significantly prevented the reduction of electroretinogram (ERG) amplitudes (a- and b-waves) caused by light exposure. nii.ac.jpnih.gov this compound also ameliorated damage to the inner and outer segments of photoreceptors and reduced the number of apoptotic cells in the outer nuclear layer. nii.ac.jpnih.gov In a rat model of laser-induced choroidal neovascularization (CNV), a model for wet AMD, this compound showed protection against CNV development. nii.ac.jp

The protective effects of this compound in these models appear to be linked to its antioxidant properties rather than solely through dopamine receptor activation. nii.ac.jpnih.gov In vitro studies using human retinal pigment epithelium cells (ARPE-19) showed that this compound suppressed hydrogen peroxide-induced cell death and prevented the intracellular accumulation of reactive oxygen species. nii.ac.jpnih.gov this compound also demonstrated direct scavenging activity towards hydroxyl radicals. nii.ac.jpnih.gov These findings suggest that this compound's antioxidant effects may contribute to its potential therapeutic value in retinal degenerative disorders like dry AMD. nii.ac.jpnih.gov

Retrospective cohort analyses have also investigated the influence of dopamine-modulating therapies, including this compound, on the conversion from dry to wet AMD in human subjects. arvojournals.orgarvojournals.org One study found that while dopamine-modulating therapies were not associated with a significantly reduced risk of conversion at 2 years, they were associated with a reduced risk of conversion at 3 and 4 years. arvojournals.org Another retrospective study comparing levodopa to other dopamine agonists (including this compound) in AMD patients observed variations in the progression of AMD between cohorts, suggesting that further investigation with larger sample sizes is warranted to ascertain the comparative effects. arvojournals.org

The (R)-enantiomer of this compound has also been explored for its potential in treating age-related macular degeneration, with preclinical evidence suggesting neuroprotective properties independent of dopamine receptor affinity. google.com

Absorption Characteristics

Pharmacokinetic studies in human subjects have characterized the absorption of this compound following oral administration. This compound is rapidly and extensively absorbed from the gastrointestinal tract. europa.eunih.goveuropa.euhpra.iedominapharm.comfda.gov

The absolute bioavailability of this compound is consistently reported as greater than 90%, indicating that it is well absorbed and undergoes minimal first-pass metabolism. europa.eunih.goveuropa.euhpra.iedominapharm.comfda.govdrugbank.comdrugs.com Peak plasma concentrations are typically attained within approximately 1 to 3 hours after oral administration of immediate-release formulations. europa.eunih.goveuropa.euhpra.iedominapharm.comfda.govdrugs.commdpi.com

The presence of food does not significantly affect the extent of this compound absorption. europa.eunih.goveuropa.euhpra.iedominapharm.comfda.govmdpi.com However, concomitant administration with food can delay the rate of absorption, resulting in a delay in the time to reach maximum plasma concentration (Tmax) by about one hour. nih.govfda.govmdpi.com

This compound exhibits linear pharmacokinetics over the clinical dosage range, with small inter-patient variation in plasma levels. europa.eunih.goveuropa.euhpra.ie

The following table summarizes key absorption characteristics of this compound:

Cardiovascular Adverse Events (e.g., orthostatic hypotension)

Cardiovascular effects, particularly orthostatic hypotension, have been documented in studies involving this compound. Orthostatic hypotension, characterized by a drop in blood pressure upon standing, has been identified as a dose-related phenomenon in some studies. fda.gov In early safety and tolerance studies, symptomatic orthostatic hypotension was a reason for discontinuation in some patients. fda.gov A meta-analysis of randomized controlled trials noted orthostatic hypotension as the most frequently reported cardiovascular outcome. mdpi.com While some preliminary analyses suggested a potential association between this compound and adverse cardiovascular reactions like heart failure and orthostatic hypotension, a pooled analysis of randomized control trials by the FDA found a non-significant increase in heart failure associated with the drug. conicet.gov.ar Despite this, the FDA released a safety announcement in 2012 regarding the potential risk of heart failure with this compound use. mdpi.comconicet.gov.ar

Impulse Control Disorders (ICDs) and Compulsive Behaviors (e.g., pathological gambling, hypersexuality, compulsive shopping, binge eating, punding)

This compound has been associated with the development of impulse control disorders (ICDs) and compulsive behaviors. These can include pathological gambling, hypersexuality, compulsive shopping, and binge eating. nih.govresearchgate.netmichaeljfox.orgpsychiatrist.comnih.gov Research indicates that these behaviors are not unique to this compound but are considered a class effect of dopamine agonists. nih.gov

Studies have investigated the prevalence of ICDs in patients treated with dopamine agonists, including this compound. A large cross-sectional study of patients with Parkinson's disease found that 13.6% had an ICD, with specific rates for pathological gambling (5%), aberrant sexual behavior (3.5%), excessive spending (5.7%), and binge eating (4.3%). nih.gov Some patients may experience multiple ICDs or concurrent compulsive behaviors like punding. researchgate.netnih.gov

The development of ICDs has also been reported in patients receiving dopamine agonists for conditions other than Parkinson's disease, such as restless legs syndrome and fibromyalgia, although typically at lower doses than those used for Parkinson's disease. nih.govresearchgate.netnih.gov In a retrospective review of fibromyalgia patients treated with dopamine agonists (over 95% on this compound), 21 out of 1356 patients were identified with compulsive gambling, shopping, or both. nih.govresearchgate.net These compulsive behaviors resolved in the majority of these patients following discontinuation of the dopamine agonist. nih.govresearchgate.net

Research suggests a link between the stimulation of dopamine D2/3 receptors, particularly in mesolimbic reward pathways, and the emergence of compulsive behaviors. researchgate.netpsychiatrist.com While the exact mechanisms are still being explored, studies have indicated that higher doses of dopamine agonists and a history of mood disorders or substance abuse may be associated with a higher risk of developing ICDs. michaeljfox.orgpsychiatrist.comnih.gov

Psychiatric Adverse Events (e.g., psychosis, manic switching, apathy, anxiety, depression)

Psychiatric adverse events, including psychosis, manic switching, apathy, anxiety, and depression, have been linked to this compound. Psychosis, particularly visual hallucinations, has been reported in patients treated with this compound, with rates varying in studies. nih.govresearchgate.netresearchgate.netpsicoestasis.com The risk of psychosis appears to be dose-related, with higher rates observed at higher doses used in Parkinson's disease compared to lower doses used for depression. researchgate.netpsicoestasis.com In some cases, psychotic symptoms have resolved with dose reduction or discontinuation of the medication. researchgate.netpsychiatryonline.org

Manic switching has been observed, particularly in patients with bipolar disorder treated with this compound. However, some studies suggest a low short-term rate of manic switching in this population. nih.govresearchgate.netresearchgate.net

Apathy, anxiety, and depression are also recognized as potential psychiatric adverse events, and these symptoms can also be part of the dopamine agonist withdrawal syndrome. europa.euconsensus.app

Dopamine Agonist Withdrawal Syndrome (DAWS)

Dopamine Agonist Withdrawal Syndrome (DAWS) is a collection of physical and psychological symptoms that can occur upon reduction or discontinuation of dopamine agonists like this compound. nih.govconsensus.app Symptoms can include apathy, anxiety, depression, fatigue, sweating, and pain. europa.euconsensus.app DAWS can be a significant source of distress and disability for patients. nih.gov

Studies have investigated the frequency and factors associated with DAWS. In studies of patients withdrawing from dopamine agonists, the frequency of DAWS has ranged from 15% to 24%. europa.eu Development of impulse control disorders has been strongly linked to DAWS, with nearly all patients experiencing DAWS having a history of ICDs in some studies. nih.govconsensus.appnih.gov Higher dopamine agonist doses at the time of withdrawal have also been identified as a significant associated factor. nih.gov DAWS can be resistant to treatment, including levodopa. consensus.appnih.gov While often self-limited, some patients may experience prolonged withdrawal or be unable to discontinue the dopamine agonist. nih.govcambridge.org

Augmentation in Restless Legs Syndrome

Augmentation is a phenomenon observed in the long-term treatment of Restless Legs Syndrome (RLS) with dopaminergic agents, including this compound. It is characterized by RLS symptoms appearing earlier in the day, increasing in intensity, or spreading to other body parts. frontiersin.orgnih.govmassgeneral.org

Research indicates that augmentation is a common complication of long-term dopamine agonist therapy for RLS. In a cohort study of patients treated with this compound for a mean of 8 years, augmentation developed in 42% of patients, typically within the first 4 years of treatment. nih.gov Another study with a mean duration of 21.2 months found augmentation in 32% of patients. nih.gov Augmentation can lead to the need for increased medication doses or the addition of other non-dopaminergic treatments. frontiersin.orgnih.govnih.gov

Hypotheses regarding the causes of augmentation in RLS suggest a link to impaired dopamine function in the central nervous system, potentially involving desensitization of dopamine receptors with chronic administration. frontiersin.org Studies have shown that patients with augmentation may have a longer duration of RLS symptoms before treatment and may require higher doses of this compound. researchgate.net

Rare and Serious Adverse Events (e.g., sleep attacks, retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, cardiac valvulopathy)

In addition to the more common adverse events, rare and serious adverse events have been associated with dopamine agonists, including this compound.

Sudden onset of sleep, or "sleep attacks," has been reported in patients taking this compound, sometimes occurring without warning signs and potentially leading to accidents. hres.camdedge.comhres.canih.gov While some patients report somnolence beforehand, others perceive themselves as alert immediately prior to falling asleep. hres.cahres.ca This can occur even after a year of treatment. nih.gov

Fibrotic complications, such as retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy, have been reported with ergot-derived dopaminergic agents. hres.camdedge.comhres.canih.govresearchgate.net Although these complications were not reported in the clinical development program for this compound, a non-ergot derivative, a small number of post-marketing reports have included possible fibrotic complications. hres.camdedge.comhres.canih.gov While the evidence is not sufficient to establish a definitive causal relationship between this compound and these fibrotic events, a contribution cannot be entirely ruled out in rare cases. hres.camdedge.comhres.canih.gov Cardiac valvulopathy, specifically, has been a concern with ergot dopamine agonists, leading to the withdrawal of some medications from the market. mdpi.comresearchgate.net

Dopamine Receptor Genes (e.g., DRD2, DRD3, DRD4, DRD5)

Polymorphisms in dopamine receptor genes, which encode the target proteins for this compound, are among the most studied genetic factors in relation to treatment response in PD. medscape.compharmgkb.org The dopamine receptors are classified into two major groups: the D1-class (D1 and D5, encoded by DRD1 and DRD5) and the D2-class (D2, D3, and D4, encoded by DRD2, DRD3, and DRD4). pharmascholars.com this compound primarily acts as an agonist at dopamine D2-like receptors, with a higher affinity for the D3 receptor.

Studies have indicated that polymorphisms in DRD2 and DRD3 may influence the clinical efficacy of this compound. mdpi.com For instance, the rs6280 SNP in DRD3 has been correlated with the response to this compound, with some studies suggesting that patients carrying the Gly/Gly genotype may require higher doses of dopamine agonists for effective treatment compared to those with the Ser/Ser genotype. semanticscholar.orgmdpi.com The Ser/Ser genotype of DRD3 Ser9Gly polymorphism has been associated with a higher response rate to dopamine agonists and potentially requiring smaller doses. semanticscholar.orgmedscape.comresearchgate.net

While DRD2 polymorphisms have also been investigated, findings regarding their specific association with this compound response have been less consistent compared to DRD3. semanticscholar.orgmdpi.com Polymorphisms in DRD1, DRD4, and DRD5 have also been explored for their potential influence on antiparkinsonian drug actions, though research specifically linking them to this compound response is less extensive. innovareacademics.inmdpi.com

Other Relevant Genes (e.g., COMT, SLC6A3)

Beyond dopamine receptors, genetic variations in enzymes involved in dopamine metabolism and transporters that regulate dopamine levels in the synaptic cleft can also impact this compound response.

The solute carrier family 6 member 3 (SLC6A3) gene encodes the dopamine transporter (DAT), which is responsible for the reuptake of dopamine from the synaptic cleft back into the presynaptic neuron. pharmascholars.com Variations in SLC6A3 can affect dopamine uptake and have been investigated in relation to response to dopaminergic treatments. pharmascholars.comnih.govpharmgkb.orgresearchgate.net While some studies have linked SLC6A3 polymorphisms to the response to levodopa, their direct influence on this compound efficacy or adverse events is an area of ongoing research. nih.govresearchgate.net

Influence on Efficacy and Adverse Events

Genetic polymorphisms can influence both the efficacy of this compound in improving symptoms and the likelihood of experiencing adverse events. The marked differences in drug response and adverse effect profiles among patients have driven the search for genetic markers that can predict an individual's response. innovareacademics.inpharmascholars.com

For instance, variations in DRD3 have been linked to the required dose of this compound for effective treatment. semanticscholar.orgmdpi.com While the focus has often been on efficacy in motor symptoms, genetic factors may also play a role in the response of non-motor symptoms, such as depression, to this compound. centerwatch.complos.orgresearchgate.net