Search results for "Valproic acid"

From the covalent linkage of drugs to novel inhibitors of ribonucleotide reductase: synthesis and biological evaluation of valproic esters of 3'-C-me…

2014

We synthesized a series of serum-stable covalently linked drugs derived from 3'-C-methyladenosine (3'-Me-Ado) and valproic acid (VPA), which are ribonucleotide reductase (RR) and histone deacetylase (HDAC) inhibitors, respectively. While the combination of free VPA and 3'-Me-Ado resulted in a clear synergistic apoptotic effect, the conjugates had lost their HDAC inhibitory effect as well as the corresponding apoptotic activity. Two of the analogs, 2',5'-bis-O-valproyl-3'-C-methyladenosine (A160) and 5'-O-valproyl-3'-C-methyladenosine (A167), showed promising cytotoxic activities against human hematological and solid cancer cell lines. A167 was less potent than A160 but had interesting featu…

'Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine

2016

Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, whil…

Liver failure under valproic acid

2011

Valproic acid (VPA, 2-propylvaleric acid) is originally an antiepileptic drug, which has been in use for more than 30 years in over 100 countries. The clinical application of VPA has expanded in the last years. Approval has been granted by the FDA for treatment of migraine and cluster headache in 1996, and for treatment of mania and long-term prophylaxis of bipolar affective disorder in 1995. In ongoing studies, VPA has been reported to inhibit growth of several types of cancer cells; in addition, effects on neurodegeneration, and on virus replication in HIV infection have been demonstrated potentially expanding the application of VPA in the future. Despite a good tolerability of the drug, …

Syndrome démentiel du sujet âgé lié à un traitement par acide valproïque : à propos d’un cas

2008

In addition to the usual adverse effects, the chronic use of the valproic acid can entail dementia syndrome. We describe the case of a 68-year-old woman who had presented a dementia syndrome due to the use of valproic acid for one year. This drug was prescribed in order to prevent a potential convulsive crisis after an ischemic stroke in a patient who did not have a history of epilepsy. This case shows that each clinician must be careful about all medications consumed by the patient in the face of cognitive disorders.

Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat

2018

Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid. Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters,…

Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents

2017

Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 6…

N-Valproyl-L-Phenylalanine as new potential antiepileptic drug: Synthesis, characterization and in vitro studies on stability, toxicity and anticonvu…

2013

Valproic acid (VPA) is considered first-line drug in treatment of generalized idiopathic seizures such as absence, generalized tonic-clonic and myoclonic seizures. Among major antiepileptic drugs, VPA is also considered effective in childhood epilepsies and infantile spasms. Due to its broad activity, VPA acts as a mood stabilizer in bipolar disorder and it is useful in migraine prophylaxis. Despite its long-standing usage, severe reactions to VPA, such as liver toxicity and teratogenicity, are reported. To circumvent side effects due to structural characteristics of VPA, we synthesized in good yield a new VPA-aminoacid conjugate, the N-valproyl-L-Phenylalanine, and characterized by FT-IR, …

Single and repeated treatment with chlordiazepoxide and sodium valproate and head-twitch responses induced in rats with rolipram, a potential antidep…

1989

Rufinamide in children and adults with Lennox-Gastaut syndrome: first Italian multicenter experience

2010

This is the first multicenter Italian experience with rufinamide as an adjunctive drug in children, adolescents and adults with Lennox-Gastaut syndrome. The patients were enrolled in a prospective, add-on, open-label treatment study from 11 Italian centers for children and adolescent epilepsy care. Forty-three patients (26 males, 17 females), aged between 4 and 34 years (mean 15.9 ± 7.3, median 15.0), were treated with rufinamide for a mean period of 12.3 months (range 3-21 months). Twenty patients were diagnosed as cryptogenic and 23 as symptomatic. Rufinamide was added to the baseline therapy at the starting dose of 10mg/kg body weight, evenly divided in two daily doses and then increased…

Effects on executive functions of antiepileptic monotherapy in pediatric age.

2020

Abstract Objectives Cognitive abilities and executive functions in children and adolescents are important indicators of quality of life as well as academic and social achievements. Cognitive and executive functioning are often impaired in patients with epilepsy and can be exacerbated by seizures and antiseizure drugs. The aim of our observational retrospective study was to assess executive functioning in patients with pediatric epilepsy, currently taking a single antiseizure medication. Materials and methods Records of 172 children and adolescents aged between 6 and 18 years (mean age = 12 ± 3.4 years) with newly diagnosed epilepsy who had not yet commenced an antiepileptic treatment were i…