Explore the vast range of titles available.

Opicapone is a novel, once-daily, potent third-generation catechol-O-methyltransferase inhibitor. We aimed to assess the safety and efficacy of opicapone as an adjunct to levodopa compared with placebo or entacapone in patients with Parkinson's disease and motor fluctuations. We did a randomised, double-blind, placebo-controlled and active-controlled trial of opicapone as an adjunct to levodopa in patients with Parkinson's disease with end-of-dose motor fluctuations. Patients aged 30–83 years were enrolled at 106 specialist centres across 19 European countries and Russia and were randomly assigned (1:1:1:1:1) by a proprietary computer-generated sequence to oral treatment with opicapone (5 mg, 25 mg, or 50 mg once daily), placebo, or entacapone (200 mg with every levodopa intake) for 14–15 weeks. Patients and investigators (ie, outcome assessors) were masked to treatment allocation. The primary endpoint was the change from baseline to end of study treatment in absolute time in the off state, as assessed by daily paper patient diaries; the primary analysis followed a hierarchical procedure for each opicapone dose in which superiority compared with placebo in the full analysis set was first tested and then, if positive, non-inferiority to entacapone was tested in the per-protocol set with a margin of 30 min. This trial is registered with EudraCT, 2010-021860-13, and ClinicalTrials.gov, NCT01568073. Between March 31, 2011, and Nov 30, 2013, of 679 patients screened, 600 were randomly assigned. 590 patients were included in the full analysis set (120 in the placebo group, 120 in the entacapone group, 119 in the opicapone 5 mg group, 116 in the opicapone 25 mg group, and 115 in the opicapone 50 mg group) and 537 in the per-protocol set (112 in the placebo group, 104 in the entacapone group, 110 in the opicapone 5 mg group, 105 in the opicapone 25 mg group, and 106 in the opicapone 50 mg group). The mean change in time in the off state was −56·0 min (SE 13·4; 95% CI −82·3 to −29·7) for placebo, −96·3 min (13·4; −122·6 to −70·0) for entacapone, −91·3 min (13·5; −117·7 to −64·8) for opicapone 5 mg, −85·9 min (13·7; −112·8 to −59·1) for opicapone 25 mg, and −116·8 min (14·0; −144·2 to −89·4) for opicapone 50 mg. Treatment with opicapone 50 mg was superior to placebo (mean difference in change from baseline −60·8 min, 95% CI −97·2 to −24·4; p=0·0015) and non-inferior to entacapone (−26·2 min, −63·8 to 11·4; p=0·0051). Treatment with opicapone 5 mg (p=0·056) or 25 mg (p=0·080) was not significantly different from treatment with placebo. Treatment-emergent adverse events were reported in 60 (50%) of 121 patients in the placebo group, 69 (57%) of 122 in the entacapone group, 63 (52%) of 122 in the opicapone 5 mg group, 65 (55%) of 119 in the opicapone 25 mg group, and 62 (54%) of 115 in the opicapone 50 mg group. The most common adverse events were dyskinesia (in five patients in the placebo group, ten in the entacapone group, 17 in the opicapone 5 mg group, nine in the opicapone 25 mg group, and 18 in the opicapone 50 mg group), insomnia (in one, seven, two, seven, and seven patients, respectively), and constipation (in three, five, four, none, and seven patients, respectively). Serious adverse events were reported in six patients in the placebo group, eight in the entacapone group, four each in the opicapone 5 mg and opicapone 50 mg groups, and one in the opicapone 25 mg group. The addition of opicapone 50 mg to levodopa treatment in patients with Parkinson's disease and end-of-dose motor fluctuations could enable a simplified drug regimen that allows physicians to individually tailor the existing levodopa daily regimen, by potentially reducing the total daily levodopa dose, increasing the dosing interval, and ultimately reducing the number of intakes, thereby maximising its benefit. BIAL.

Rasagiline mesylate is a novel drug for Parkinson's disease with selective, irreversible monoamine oxidase B (MAO-B) inhibitor activity, and is effective as monotherapy in early disease. This study investigated rasagiline efficacy and safety in levodopa-treated patients with Parkinson's disease and motor fluctuations. In an 18-week, double-blind, multicentre (74 hospitals and academic centres in Israel, Argentina, and Europe) trial, 687 outpatients were randomly assigned to oral rasagiline (231 individuals; 1 mg once daily), entacapone (227; 200 mg with every levodopa dose), or placebo (229). Primary outcome was change in total daily off-time (intention-to-treat population). Other measures included the clinical global improvement (CGI) score and unified Parkinson's disease rating scale (UPDRS) scores. Analysis was by intention to treat. 88 (13%) patients who were assigned treatment did not complete the study (23 rasagiline, 30 entacapone, 35 placebo), mainly because of withdrawal of consent (n=34) and adverse events (n=34). Both rasagiline and entacapone reduced mean daily off-time (–1·18 h rasagiline and –1·2 h entacapone vs placebo –0·4 h; p=0·0001, p<0·0001, respectively) and increased daily on-time without troublesome dyskinesia (0·85 h vs placebo 0·03 h; p=0·0005 for both). We recorded significant mean improvements in CGI scores (–0·86 rasagiline and –0·72 entacapone vs –0·37 placebo; p<0·0001, p=0·0002, respectively). Changes in UPDRS scores also significantly improved for activities of daily living during off-time (–1·71 and –1·38 vs placebo; p<0·0001, p=0·0006, respectively) and motor function during on-time (–2·94 and –2·73 vs placebo; both p<0·0001). Frequency of adverse events was similar for all treatments. Once-daily rasagiline reduces mean daily off-time and improves symptoms of Parkinson's disease in levodopa-treated patients with motor fluctuations, an effect similar to that of entacapone.

Background Migraine is a highly prevalent neurological disorder related to severe, unilateral headache and symptoms such as vomiting, nausea, and photophobia. Growing evidence implicates oxidative stress and inflammation as key contributors to migraine pathophysiology, exacerbating symptoms and related mental health conditions. Mixodin is a novel bioactive formulation derived from natural compounds, including curcumin, piperine, and gingerol, which are well-established for their anti-inflammatory and antioxidant properties. While each component has shown potential in alleviating migraine-related symptoms, the combined therapeutic efficacy remains unclear. This study investigates whether the combined natural compounds in mixodin provide synergistic benefits in migraine management by targeting multiple underlying mechanisms. This study aims to examine the effects of mixodin supplementation on clinical symptoms, mental health, quality of life (QOL), inflammatory, and oxidative stress factors in patients with migraine. Methods This study is a randomized, double-blind, placebo-controlled clinical trial involving 60 patients diagnosed with migraine by a neurologist according to the ICHD-3 criteria. Eligible participants, aged 20 to 60 years, will be randomly assigned to one of two groups. The intervention group ( n  = 30) will receive two mixodin capsules daily for 8 weeks, each containing 300 mg of curcumin, 7.5 mg of gingerol, and 3.75 mg of piperine. The control group ( n  = 30) will receive two placebo capsules daily for the same duration. The primary outcome will be the clinical symptoms of migraine, including the frequency, severity, and duration of migraine attacks reported by patients. Secondary outcomes will include serum levels of high-sensitivity C-reactive protein (hs-CRP), calcitonin gene-related peptide (CGRP), total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and assessments of mental health status and QOL. Discussion This clinical trial aims to evaluate the effects of mixodin supplementation on inflammatory markers, oxidative stress, migraine-related symptoms, mental health, and QOL in patients with migraine. The results may suggestion insights into underlying mechanisms and support the development of evidence-based clinical guidelines that incorporate anti-inflammatory and antioxidant strategies to enhance therapeutic outcomes in migraine management. Trial registration Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20241009063312N1). Registration date: 2024–12–15. Trial status The protocol is Version 2.0, March 01, 2025. Recruitment began November 11, 2024, and is anticipated to be completed by June 22, 2025.

Background Entacapone has been widely used in the treatment of moderate to advanced Parkinson’s disease (PD), and its efficacy for motor symptoms has been well-known from several clinical trials and long-term clinical use. The efficacy of Levodopa/Carbidopa/Entacapone (LCE) on neuropsychological functions in moderate to advanced PD has not been validated yet, and little is known about the effect of LCE on peripheral inflammatory cytokines. Objectives The aim of this study was to investigate the efficacy of LCE on neuropsychological functions in moderate to advanced PD and to explore its relationship with the changes in peripheral inflammatory cytokine levels. Methods All patients were randomly assigned to the experimental group receiving treatment of LCE or the control group receiving treatment of Levodopa/Carbidopa (LC). All patients were clinically evaluated using the Unified Parkinson’s Disease Rating Scale part III (UPDRS III), the total score of the Parkinson’s Disease Questionnaire-39 (PDQ-39), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD), and serum homocysteine (HCY) as well as serum inflammatory cytokines were measured at baseline and after 8 weeks. Results The moderate to advanced PD patients treated with LCE had more significant improvement in MMSE scores ( P  = 0.004) and MoCA scores ( P  = 0.001), as well as a greater decline in IL-6 levels ( P  = 0.002) than those treated with LC. There were no significant differences in the changes of the UPDRS III, PDQ39, HAMA, and HAMD scores between the two treatment groups. Linear correlation analysis revealed that there was a significant negative correlation between the improvement of MoCA scores (ΔMoCA) and the reduction of IL-6 levels (ΔIL-6) (correlation coefficient: -0.252; P  = 0.024). Conclusions The ability of LCE to improve cognitive function and to downregulate the peripheral inflammatory cytokine IL-6 levels in moderate to advanced PD is superior to the traditional dopamine preparation—LC. LCE may improve cognitive function by suppressing the levels of inflammatory cytokines like IL-6. Trial registration The full name of the registry: Dongyang People’s Hospital, Affiliated to Wenzhou Medical University. The trial registration number (TRN): ChiCTR2400091631. The date of registration: October 31, 2024 (Retrospectively registered).

Objectives To compare plasma levodopa concentrations after repeated doses of levodopa/carbidopa/entacapone (LCE) and levodopa/carbidopa (LC). Methods Open-label, randomized, two-period, active-controlled, cross-over study with four dosing regimens: groups I and II (healthy volunteers and Parkinson's disease patients) received levodopa 100 mg or 150 mg four times daily, respectively, and groups III and IV (healthy volunteers) received the same strengths of levodopa five times daily. Pharmacokinetic (PK) parameters determined for levodopa included Cmin, Cmax, Cmax - Cmin, AUC, t₁/₂, and tmax. Results In healthy volunteers and PD patients, mean trough levels (Cmin), Cmax, and AUC of levodopa were, in general, significantly higher during LCE compared to LC administration. Compared to Cmin, Cmax, and AUC, differences between the treatments in variability of levodopa concentrations (Cmax - Cmin) were less consistent. Conclusions The present results on the differences in levodopa PK between LCE and LC provide a basis to evaluate the relationship of levodopa PK and the induction of motor complications in an on-going study in early Parkinson's disease using similar dosing regimens.

Objective: To study the effect of entacapone, a specific peripherally acting catechol-O-methyltransferase (COMT) inhibitor used in combination with levodopa treatment, in cases of Parkinson’s disease with both fluctuating and non-fluctuating response to treatment. Methods: A randomised, placebo controlled, double blind, six month study was undertaken in 172 fluctuating and 128 non-fluctuating patients. The clinical efficacy and safety of 200 mg entacapone given with each daily levodopa dose was studied. Efficacy was examined using home diaries, the unified Parkinson disease rating scale (UPDRS), and recording of daily levodopa dose. Results: The primary efficacy variable for fluctuating patients—the proportion of daily ON time—showed a significant increase compared with placebo (p < 0.05). The absolute ON time (mean (SD)) increased from 9.5 (2.5) to 10.8 (2.4) hours (p < 0.01), and the daily OFF time was correspondingly reduced from 7.0 (2.6) to 5.9 (2.5) hours (p < 0.05 v placebo). This improvement was achieved despite a reduction in daily levodopa requirements. The effect was rapidly lost on withdrawal of entacapone. In non-fluctuating patients, the primary efficacy measure was part II of the UPDRS (activities of daily living; ADL). In this group of patients, ADL scores improved in the entacapone group (p < 0.01 v placebo), and there was also a 40 mg reduction in levodopa requirement (p < 0.01 v placebo). Entacapone was well tolerated by both fluctuating and non-fluctuating patients. Conclusions: The ability of entacapone to provide additional benefits to levodopa treatment in increasing ON time in fluctuating Parkinson’s disease patients was confirmed. A novel finding was that patients without fluctuations also obtained benefit from the addition of entacapone to their levodopa treatment, as evidenced by improved ADL scores and a relatively reduced levodopa requirement.

Negative symptoms in schizophrenia are associated with decreased dopaminergic activity in the prefrontal cortex (PFC). It is hypothesized that increasing dopamine levels would alleviate negative symptoms. Termination of dopamine activity in the PFC is mainly via catechol-O-methyl tranferase (COMT) activity. Hence, inhibition of COMT activity with entacapone should reverse PFC dopaminergic transmission. To assess the efficacy of entacapone addition to antipsychotic treatment in patients with residual schizophrenia, we conducted a double-blind, randomised, placebo-controlled study for 12 wk of treatment with entacapone or placebo. Clinical measures (PANSS, CGI and QLS) were obtained at baseline and at weeks 4, 8 and 12 and cognitive functions were assessed by the RBANSS. Significant improvement over time in PANSS and QLS scores was observed in both groups. However, entacapone did not demonstrate a beneficial effect compared to placebo. Therefore, this study does not support a therapeutic role for entacapone in residual schizophrenia.

Background Repeated dosing of levodopa/carbidopa/entacapone (LCE) has shown a favourable pharmacokinetic (PK) profile compared with levodopa/carbidopa (LC), but increases maximum plasma levodopa concentrations (C max ) during the day. High levodopa concentrations are associated with peak-dose dyskinesias. Purpose To determine whether administering LCE 75/18.5/200 and 125/31.5/200 mg (LCE 75 and LCE 125) following a morning dose of LCE 100/25/200 and 150/37.5/200 mg (LCE 100 and LCE 150), respectively, would avoid the increase in levodopa C max values observed during multiple dosing of LCE 100 and LCE 150. Methods This was an open, randomized, three-period, crossover PK trial in healthy volunteers ( n  = 19). Subjects were randomized to Group 1 or 2. Group 1 received in random sequence: LCE 150 followed by LCE 125 three times daily (tid); LCE 150 four times daily (qid); LC 150 qid. Group 2 received in random sequence: LCE 100 followed by LCE 75 tid; LCE 100 qid; LC 100 qid. Levodopa C max , minimum plasma concentration (C min ), area under the curve (AUC 0−14 ) and peak–trough fluctuation (PTF) were calculated up to 14 h after the first dose. Results Levodopa C max was not increased when the LCE dose was decreased by 25 mg after the morning dose. In comparison to LC, levodopa C min levels and AUC 0−14 values for LCE were significantly higher, while the levodopa PTF was significantly smaller. Conclusions Reducing the dose of LCE by 25 mg following the first morning dose results in a more consistent levodopa C max profile, avoiding levodopa accumulation while maintaining significantly higher C min levels and AUC 0−14 values compared with LC.

is an opportunistic pathogen and responsible for candidiasis. readily forms biofilms on various biotic and abiotic surfaces, and these biofilms can cause local and systemic infections. biofilms are more resistant than its free yeast to antifungal agents and less affected by host immune responses. Transition of yeast cells to hyphal cells is required for biofilm formation and is believed to be a crucial virulence factor. In this study, six components of ginger were investigated for antibiofilm and antivirulence activities against a fluconazole-resistant strain. It was found 6-gingerol, 8-gingerol, and 6-shogaol effectively inhibited biofilm formation. In particular, 6-shogaol at 10 μg/ml significantly reduced biofilm formation but had no effect on planktonic cell growth. Also, 6-gingerol and 6-shogaol inhibited hyphal growth in embedded colonies and free-living planktonic cells, and prevented cell aggregation. Furthermore, 6-gingerol and 6-shogaol reduced virulence in a nematode infection model without causing toxicity at the tested concentrations. Transcriptomic analysis using RNA-seq and qRT-PCR showed 6-gingerol and 6-shogaol induced several transporters ( , and ), but repressed the expressions of several hypha/biofilm related genes ( and ), which supported observed phenotypic changes. These results highlight the antibiofilm and antivirulence activities of the ginger components, 6-gingerol and 6-shogaol, against a drug resistant strain.

Gingerols and shogaols are recognized as active ingredients in ginger and exhibit diverse pharmacological activities. The preclinical pharmacokinetics and tissue distribution investigations of gingerols and shogaols in rats remain less explored, especially for the simultaneous analysis of multi-components. In this study, a rapid, sensitive, selective, and reliable method using an Ultra-Performance Liquid Chromatography Q-Exactive High-Resolution Mass Spectrometer (UPLC-Q-Exactive–HRMS) was established and validated for simultaneous determination of eight compounds, including 6-gingerol, 6-shogaol, 8-gingerol, 8-shogaol, 10-gingerol, 10-shogaol, Zingerone, and 6-isodehydrogingenone in plasma and tissues of rats. The analytes were separated on a Syncronis C18 column (100 × 2.1 mm, 1.7 µm) using a gradient elution of acetonitrile and 0.1% formic acid in water at a flow rate of 0.25 mL/min at 30 °C. The method was linear for each ingredient over the investigated range with all correlation coefficients greater than 0.9910. The lowest Lower Limit of quantitation (LLOQ) was 1.0 ng/mL. The intra- and inter-day precisions (Relative Standard Deviation, RSD%) were less than 12.2% and the accuracy (relative error, RE%) ranged from −8.7% to 8.7%. Extraction recovery was 91.4–107.4% and the matrix effect was 86.3–113.4%. The validated method was successfully applied to investigate the pharmacokinetics and tissue distribution of eight components after oral administration of ginger extract to rats. These results provide useful information about the pharmacokinetics and biodistribution of the multi-component bioactive ingredients of ginger in rats and will contribute to clinical practice and the evaluation of the safety of a Chinese herbal medicine.