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Oxalate is a metabolite promoting the formation of calcium oxalate crystals in urine. Hyperoxaluria is a feature of genetic diseases, known as primary hyperoxaluria, leading to chronic kidney disease. Ethylene glycol poisoning induces the crystallization of calcium oxalate crystals in renal tubules, promoting acute renal failure. Urine oxalate results from glyoxylate transformation to oxalate in the liver, due to lactate dehydrogenase (LDH) activity, especially the LDH-5 isoenzyme. Genetic RNA interference therapy targeting lactate dehydrogenase lowers urine oxalate excretion in murine models. Stiripentol is a drug inhibiting neuronal LDH-5 isoenzyme activity. We hypothesized that stiripentol would also reduce hepatic oxalate production and urine oxalate excretion. In vitro Stiripentol decreases oxalate synthesis by hepatocytes. In vivo, stiripentol decreases urine oxalate excretion in rats and protects kidney tissue and function against ethylene glycol intoxication and hydroxyproline-induced calcium oxalate crystalline nephropathy. The use of stiripentol in clinical practice deserves further clinical studies.

Nucleoside analogues are commonly used in the treatment of hematological malignancies and solid tumors. As antimetabolites, these drugs act by disrupting DNA synthesis and inducing apoptosis following their incorporation into DNA. Troxacitabine (Troxatyl) is the first nucleoside analogue with anticancer activity that has an unnatural stereochemical configuration. Its broad preclinical antineoplastic spectrum led to its clinical development. Summaries of the preclinical data and of the initial phase I and II clinical trials are presented.

To describe the long term efficacy and tolerance of stiripentol associated with valproate and clobazam in an exhaustive cohort of patients with severe myoclonic epilepsy of infancy (Dravet's syndrome), in which short term efficacy of such a treatment has recently been demonstrated in a placebo-controlled trial.In 46 patients the frequency and the duration of seizures was significantly reduced (p0.001) as well as the number of convulsive status at a median of three-year follow-up. Ten patients were dramatically improved (seizures significantly decreased in number [p = 0.002] and duration [p = 0.002] and status epilepticus disappeared), 20 were moderately improved (seizures significantly decreased in duration [p = 0.001] and status were less numerous), four had no response and efficacy was non evaluable in 12 mainly because of adverse events. Efficacy was better in the youngest patients. The most frequent adverse events were loss of appetite and loss of weight. They could be so severe in patients over 12 years of age that the stiripentol dosage could not be increased to 50 mg kg-1 j-1.This follow-up study shows that stiripentol added to valproate and clobazam maintains its efficacy at long term in children with severe myoclonic epilepsy of infancy and suggests that the tritherapy should be introduced as early as possible in these patients in order to suppress the convulsive status epilepticus.

The radioactive constituents of blood, urine, and bile specimens from Wistar Rats, following intravenous administration of 3H-stiripentol were analyzed, in parallel with samples of: liver, lung, kidneys, testis, heart, brain, cerebellum, and medulla. These investigations yielded the following results: 3H-Stiripentol was quantitatively and rapidly absorbed and metabolized by Wistar rats, due to intense metabolism in the liver. The cerebellum and medulla accumulated radioactivity, which was probably related to the pharmacological effects of this drug.

Glycerolformal is not devoid of action on mice psychomotor behaviour. Administered through the digestive tract with infralethal doses, it can exercice depressing effects on muscular strength and sensitivity to pain without affecting inquisitiveness. It opposes the stimulating effects specific to pentetrazol, amphetamine and apomorphine and is a protection against electric convulsions but tends to increase the toxicity of tryptamine.