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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)
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)
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)
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)
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)
After i.v. and oral doses of estazolam (5 mg/kg) to mice, the drug was rapidly cleared with a beta half-life (t1/2 beta) of 0.7 h. The active metabolite, 1-oxo-estazolam, was present in traces in mouse plasma and brain. Its elimination t1/2 (beta), determined after i.v. injection of 1-oxo-estazolam (5 mg/kg) to mice, was similar to that of the parent drug(More)
The antileptazol effect of clobazam lasts longer in the mouse than in the rat. After intraperitoneal injection of clobazam (10 mg kg-1) plasma and brain concentrations of the drug and its rate of disappearance were similar in both species, whereas the metabolite N-demethylclobazam was present at higher concentrations and for longer in the mouse than in the(More)
The kinetic profiles and antileptazol activity of clobazam and its main metabolite were compared to assess the metabolite's contribution to the anticonvulsant activity of clobazam in the guinea-pig. The metabolite was less effective than the parent compound in terms of doses and active brain levels. However, the metabolite formed after clobazam(More)