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Journal of Neural Transmission (Vienna,... Jun 2023Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong... (Review)
Review
Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong its effect in striatal dopaminergic neurotransmission in Parkinson's disease patients. While selegiline/rasagiline and tolcapone/entacapone have been available on the market for more than one decade, safinamide and opicapone have been approved in 2015 and 2016, respectively. Meanwhile, comprehensive data from several post-authorization studies have described the use and specific characteristics of the individual substances in clinical practice under real-life conditions. Here, we summarize current knowledge on both medication classes, with a focus on the added clinical value in Parkinson's disease. Furthermore, we outline practical considerations in the treatment of motor fluctuations and provide an outlook on ongoing studies with MAO-B and COMT inhibitors.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Monoamine Oxidase; Catechol O-Methyltransferase; Levodopa; Catechol O-Methyltransferase Inhibitors; Monoamine Oxidase Inhibitors
PubMed: 36964457
DOI: 10.1007/s00702-023-02623-8 -
Circulation Research May 2021Often considered a rare disease, cardiac amyloidosis is increasingly recognized by practicing clinicians. The increased rate of diagnosis is in part due the aging of the... (Review)
Review
Often considered a rare disease, cardiac amyloidosis is increasingly recognized by practicing clinicians. The increased rate of diagnosis is in part due the aging of the population and increasing incidence and prevalence of cardiac amyloidosis with advancing age, as well as the advent of noninvasive methods using nuclear scintigraphy to diagnose transthyretin cardiac amyloidosis due to either variant or wild type transthyretin without a biopsy. Perhaps the most important driver of the increased awareness is the elucidation of the biologic mechanisms underlying the pathogenesis of cardiac amyloidosis which have led to the development of several effective therapies with differing mechanisms of actions. In this review, the mechanisms underlying the pathogenesis of cardiac amyloidosis due to light chain (AL) or transthyretin (ATTR) amyloidosis are delineated as well as the rapidly evolving therapeutic landscape that has emerged from a better pathophysiologic understanding of disease development.
Topics: Aging; Alkylating Agents; Amyloid; Amyloid Neuropathies, Familial; Amyloidosis; Antibodies, Monoclonal; Benzoates; Benzoxazoles; Bridged Bicyclo Compounds, Heterocyclic; Cardiomyopathies; Catechol O-Methyltransferase Inhibitors; Heart Transplantation; Humans; Immunomodulating Agents; Oligonucleotides; Proteasome Inhibitors; Protein Folding; Pyrazoles; RNA, Small Interfering; Stem Cell Transplantation; Sulfonamides; Tolcapone
PubMed: 33983835
DOI: 10.1161/CIRCRESAHA.121.318187 -
European Heart Journal Supplements :... Nov 2022The therapy of transthyretin (TTR)-related cardiac amyloidosis consists, on the one hand, of the prevention and management of complications (supportive therapy) and on...
The therapy of transthyretin (TTR)-related cardiac amyloidosis consists, on the one hand, of the prevention and management of complications (supportive therapy) and on the other of treatments aimed at interrupting or slowing down the production and deposition of fibrils (disease-modifying therapy). This definition includes drugs that act on different phases of amyloidogenesis: (i) silencing of the gene encoding TTR (small interfering RNA: patisiran, vutrisiran; antisense oligonucleotides: inotersen, eplontersen; new CRISPR Cas-9 drug technology for editing DNA); (ii) stabilization of circulating TTR to inhibit its dissociation and subsequent assembly of the resulting monomers in amyloidotic fibrils (tafamidis, acoramidis, and tolcapone); (iii) destruction and re-absorption of already formed amyloid tissue deposits. Drugs related to the latter strategy (antibodies) are still the subject of Phase 1 or 2 studies.
PubMed: 36380794
DOI: 10.1093/eurheartjsupp/suac104 -
Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
Neuropsychiatric Disease and Treatment 2022COMT (catechol--methyltransferase) inhibitors are key therapeutic agents in the management of motor fluctuations (MF) in patients with Parkinson's disease (PD). As... (Review)
Review
COMT (catechol--methyltransferase) inhibitors are key therapeutic agents in the management of motor fluctuations (MF) in patients with Parkinson's disease (PD). As levodopa/DDCI add-on therapy, their main benefit lies in increasing ON-time and reducing OFF-time for PD patients in the middle stages of the disease. Two of the three available COMT inhibitors, tolcapone and entacapone, have been approved for over two decades. Opicapone, a third-generation COMT inhibitor approved in 2016, was designed with the aim of overcoming specific challenges of the earlier generation compounds, specifically hepatotoxicity and short effect duration. This review aims at highlighting the specific properties and characteristics of opicapone, namely combining efficacy with good tolerability as demonstrated in the registration studies and since then confirmed under real-world conditions. Opicapone has been shown to be effective in patients with early, as well as late motor fluctuations. Whilst patients in the earlier Hoehn and Yahr stages benefit more than patients in later stages, the incidence of dyskinesia in patients with recent onset MF is around half that of patients with more established fluctuations. With the added advantage of a once-daily administration, this particular COMT inhibitor provides a simple, yet effective therapy for patients with Parkinson's disease and MF.
PubMed: 35968514
DOI: 10.2147/NDT.S279362 -
Journal of Experimental Pharmacology 2020Treatment-resistance is a frequent condition for obsessive-compulsive disorder (OCD). Over the past decades, a lot of effort has been made to address this issue, and... (Review)
Review
Treatment-resistance is a frequent condition for obsessive-compulsive disorder (OCD). Over the past decades, a lot of effort has been made to address this issue, and several augmentation strategies of serotonergic drugs have been investigated. Antidopaminergic drugs are considered the first choice as augmentation strategy for treatment-resistant OCD patients, but they seem to work only for a subset of patients, and none of them have been officially approved for OCD. Recently, the role of glutamate and inflammation in OCD pathophysiology clearly emerged, and this has led to several investigations on glutamatergic and anti-inflammatory agents. Results seem promising but still inconclusive. Probiotic interventions (considered to modulate the immune systems and the brain activity) are gaining attention in several psychiatric fields but are still at their early stages in the OCD field. Research on new treatment approaches for OCD is moving forward, and more than one hundred interventional trials are ongoing around the world. While the vast majority of these trials involve neuromodulation and psychotherapeutic approaches, only a small proportion (around 20%) involve the investigation of new pharmacological approaches (tolcapone, nabilone, psilocybin, troriluzole, nitrous oxide, rituximab, naproxen, and immunoglobulins). Here, we provide a comprehensive review of investigational and experimental drugs to treat OCD.
PubMed: 33447096
DOI: 10.2147/JEP.S255375 -
Healthcare (Basel, Switzerland) Apr 2023Temporal 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... (Review)
Review
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.
PubMed: 37046974
DOI: 10.3390/healthcare11071046