Tolcapone 100mg tablets

Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.

Abstract licence: CC BY

Background and objectivesQuality of life (QoL) is a critical outcome in the management of Parkinson's disease (PD), and is often affected more by non-motor symptoms (NMS) than motor features. While monoamine oxidase-B (MAO-B) and catechol-O-methyltransferase (COMT) inhibitors are commonly used with levodopa, their comparative impacts on QoL remains unclear. This study aimed to compare the effects of MAO-B and COMT inhibitors on global and domain-specific QoL in patients with PD using a Bayesian network meta-analysis (NMA).MethodsA comprehensive literature search was conducted using PubMed/Medline, Cochrane Library and Embase databases from the inception through April 30, 2025. Randomized controlled trials evaluating QoL using PDQ-39 or PDQ-8 in patients treated with MAO-B inhibitors (rasagiline, selegiline, safinamide) or COMT inhibitors (entacapone, opicapone, tolcapone) were included. A Bayesian NMA was performed using the "gemtc" package in R. Treatment effects were expressed as standardized mean differences (SMDs) with 95% credible intervals (CrIs). Treatment ranking was estimated using surface under the cumulative ranking curve (SUCRA) values.ResultsSixteen RCTs comprised of 3,802 patients were included. The combination of extended-release rasagiline and pramipexole (P2B001) showed the most significant improvement in global QoL (SMD = -4.16; 95% CrI: -7.24 to -1.05), followed by rasagiline monotherapy (SMD = -2.38; 95% CrI: -4.32 to -0.42). Safinamide 100 mg significantly improved emotional well-being (SMD = -2.56; 95% CrI: -5.13 to -0.04). SUCRA rankings confirmed the superior probability of benefits for rasagiline-based interventions across multiple QoL dimensions.ConclusionThis network meta-analysis provides evidence that MAO-B inhibitors, particularly rasagiline and safinamide, may offer broader QoL benefits in patients with PD, especially in NMS such as emotional well-being. These findings support a more symptom-oriented and individualized treatment approach should be provided to patients with PD. Further well-designed head-to-head studies using standardized QoL measures and extended follow-up are needed to confirm these findings and guide clinical practice.Systematic review registrationRegistered in PROSPERO (CRD420251013028): https://www.crd.york.ac.uk/PROSPERO/view/CRD420251013028.

Abstract licence: CC BY

An important aim in long-term levodopa therapy is to prolong the duration of symptomatic efficacy of each dose without increasing peak plasma concentrations above the threshold for the emergence of dyskinesias. One strategy is to enhance levodopa delivery to the brain by co-administering it with inhibitors of peripheral dopa-decarboxylase and catechol-O-methyltransferase (COMT). Levodopa, carbidopa and entacapone (LCE), available in a range of fixed-dose combinations as the branded formulation Stalevo® (Orion Pharma), has been developed to address this requirement and has been in general use for 20 years, having first been evaluated in randomized controlled trials. Experience with LCE has established that improved levodopa pharmacokinetics achieved with dual-enzyme inhibition are translated into improved clinical efficacy, including the possibility of reducing total levodopa dosage with no loss of therapeutic effect. The ease and tolerability of switching to LCE has been affirmed in the SIMCOM trial and by personal experience detailed in this review. Some 300,000 patient-years of safety data are available for LCE, including trial data for up to 5 years. Most adverse effects associated with LCE are attributable to the levodopa component rather than the enzyme inhibitors. The hepatotoxicity observed with the class comparator tolcapone has not been observed with entacapone, the COMT inhibitor in LCE, and there is no formal requirement to monitor liver function during LCE therapy. Other common side effects include diarrhoea, which is one of the more prominent non-dopaminergic adverse events, and urine discolouration, which is harmless but about which patients may require reassurance.

Abstract licence: Public domain