Trimetazidine (S 50 16), a molecule developed by the Servier Research Institute, is a cellular anti-ischemic agent. Its chemical name is I -(2,3,4-trimethoxybenzyl)-piperazine dihydrochloride (Fig. I ). Initial pharmacological studies have indicated that trimetazidine prevents cellular changes associated with ischemia or hypoxia, but it has no effect under normoxic conditions ( I ,2).Trimetazidine is freely soluble in water (80%), sparingly soluble in methanol, but insoluble in other organic solvents. Trimetazidine solution is slightly sensitive to light although substantially less than dihydropyridines. The molecular weight of tnmetazidine is, as a dihydrochloride, 339.27 and, in basic form, 266.34. The molecule has two pKa values (4.32 and 8.95) and the pH value of an aqueous solution (5 mg/ml) is 3; this aqueous solution is stable at room temperature. PHARMACOLOGY Effects on the Hypoxic Cell and on the Ischemic TissueIschemia is defined as a deficiency of blood supply in a given tissue, and consequently of oxygen supply to the cells. Ischemia results in a decrease of oxidative metabolism that is responsible for the various functional disorders observed in the cell: reduction in the production of energetic compounds, accumulation of protons, and increase in the generation of oxygen-derived free radicals. The aggression of oxygenderived free radicals towards living tissues is therefore superimposed on the energy disorders and added to the effects of acidosis, which severely alters cellular homeostasis and results in accumulation of calcium within the cell. This considerable excess of intracellular calcium blocks all vital enzymatic functions, leading to necrosis.Despite hypoxia or induced ischemia, trimetazidine maintains homeostasis and cellular functions and inhibits cytolysis. This activity has been evidenced in vivo, by Camilleri and Joseph (3), Fitoussi et al. (4), and Catroux et al. ( 5 ) , using different models of ischemia. After induction of left ventricular infarction in the rat by coro-

Various 2-benzodioxinylaminoethanol derivatives were synthetized and investigated for beta-adrenergic blocking activity. Most compounds demonstrated a beta-blocking activity of a competitive type when evaluated in guinea pig atrial and tracheal preparations. Three compounds were more potent than practolol and propranolol. All compounds demonstrated antihypertensive properties in spontaneously hypertensive rats. The most active compound was 1-(1,4-benzodioxin-2-yl)-2-[N4-(2-methoxyphenyl)piperazino]ethanol (11), which at 2.5 mg/kg iv lowered blood pressure by 41%.

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.

To evaluate blood pressure reactivity in children and its changes in adolescents, the acute pressor response to a video-game stress test and the noninvasive ambulatory blood pressure monitoring were evaluated in 62 healthy children divided into three age groups. Basal blood pressure values were measured according to the NIH Task Force. With baseline measures and body mass index controlled for, analysis of covariance showed that the video game provoked significant and incremental cardiovascular reactivity across the games in adolescents when compared with the two other groups of children. The same group of children showed also a significantly higher systolic ambulatory pressure during the daytime, whereas no significant difference was observed by basal BP measurement. In conclusion an increased reactivity to external stimuli was observed in adolescents, and this pattern was strictly associated with a higher daily blood pressure.