Giovanna Guiso

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The causes and mechanisms underlying multidrug resistance (MDR) in epilepsy are still elusive and may depend on inadequate drug concentration in crucial brain areas. We studied whether limbic seizures or anticonvulsant drug treatments in rodents enhance the brain expression of the MDR gene (mdr) encoding a permeability glycoprotein (P-gp) involved in MDR to(More)
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder involving the selective degeneration of motor neurons. In a small proportion of patients, ALS is caused by mutations in copper/zinc superoxide dismutase (SOD1), and mice overexpressing SOD1(G93A) mutant develop a syndrome that closely resembles the human disease. Excitotoxicity mediated by(More)
The present study compares the anorectic activity of d-fenfluramine and its metabolite d-norfenfluramine in three animal species. d-Fenfluramine and d-norfenfluramine show anorectic activity at increasing doses (ED50) in rats, guinea pigs, and mice, d-norfenfluramine being more active than d-fenfluramine in all three species. Equiactive anorectic activities(More)
After single oral doses of racemic fenfluramine to man and animals (male CD-COBS Sprague-Dawley rat, male CD1-COBS mice and male beagle dogs) plasma and/or brain concentrations of the d- and l-isomers and their deethylated metabolite were measured by gas-liquid chromatography. In rat and mouse d-fenfluramine had a longer half-life (T 1/2) and gave a larger(More)
1-(2-Pyrimidinyl)-piperazine (PmP) is a common metabolite of the structurally related drugs buspirone, MJ-13805 and piribedil. After i.v. injection (25 mumol/kg) to rats, all three parent drugs are rapidly cleared with a t 1/2 (beta) of about 30 min. The metabolite t 1/2 is about four times that of its parent drugs. About 25, 23 and 2% of buspirone,(More)
On irradiation with short-wavelength ultraviolet light, the potential memory-enhancing compound CL 275,838 (I) and its desbenzyl derivative CL 286,527 (metabolite II) are cleaved into the highly fluorescent derivative CL 228,346 (metabolite IV). This reaction was exploited for the sensitive and selective detection of these compounds in human and animal(More)
1. The disposition of (-)-fenfluramine, (-)-F, was studied in rats after i.v. and oral administration (1.25 to 12.5 mg/kg). Whole blood-to-plasma ratio and the protein binding (determined by equilibrium dialysis) of the compound and its main active metabolite, (-)-norfenfluramine (-)-NF, were investigated. 2. The bound fraction of both compounds (about 40%)(More)
We investigated in rats whether aspartame intake affected the susceptibility to seizures induced chemically (metrazol, quinolinic acid) or electrically (electroshock). Aspartame (0.75-1.0 g/kg), given orally as a single bolus to 16-hr fasted animals 60 min before metrazol, significantly increased the number of animals showing clonic-tonic seizures. At 1.0(More)
PURPOSE We measured the brain-to-plasma partition of 10,11-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5-carboxamide (10-OHCBZ) in epilepsy patients undergoing surgery to alleviate drug-resistant seizures and administered with different oral doses of oxcarbazepine (OXC). We addressed the possible contribution of the multidrug transporter P-glycoprotein (P-gp(More)
Oxidative stress and mitochondrial impairment are the main pathogenic mechanisms of Amyotrophic Lateral Sclerosis (ALS), a severe neurodegenerative disease still lacking of effective therapy. Recently, the coenzyme-Q (CoQ) complex, a key component of mitochondrial function and redox-state modulator, has raised interest for ALS treatment. However, while the(More)