Carnitine optical isomers' action on the epinephrine stress induced in the isolated perfused rabbit heart.

A cardiac stress was performed in the isolated perfused rabbit heart by means of four injections of 0.5 micrograms epinephrine in the coronary vessels. The endogenous (-)carnitine/acetyl(-)carnitine ratio was also determined. The two exogenous optical isomers of carnitine possess a different pharmacological behavior on the epinephrine-induced stress. Exogenous (-)carnitine reduces the epinephrine stimulating effect whereas exogenous (+)carnitine increases it, including coronary flow. Furthermore, the endogenous (-)carnitine restores this ratio to the normal value, whereas exogenous (+)carnitine does not. It is concluded that carnitine might represent an important natural way for organism safeguard in the epinephrine stress as occurs in various emotional states. In this respect the importance of exogenous (-)carnitine as a therapeutic means remains to be investigated.

RNA and protein synthesis in rat brain during exercise. Effect of arginine and some phosphorylated amino acids.

RNA and protein synthesis is noticeably depressed in the brain of swimming rats. Repeated oral administration of phosphothreonine, phosphoserine or arginine is susceptible of improving brain macromolecular synthesis. A parallel induction is observed on spermine and spermidine accumulation, particularly evident when arginine is used. The anti-fatigue effect of phosphorylated amino acids or arginine may be associated with the observed restoration of brain macromolecular synthesis via polyamine accumulation.

Teratological study of etoperidone in the rat and rabbit.

Etoperidone was administered to pregnant rats and rabbits during the period of organogenesis. The oral doses were 100 and 300 mg/kg in the rat and 5, 25 and 50 mg/kg in the rabbit. In the rat the dose of 300 mg/kg produced toxic effects on the mother, consisting mainly of behavioural changes and death in some cases; a slight increase in embryofetal mortality was also observed. The dose of 100 mg/kg still produced behavioural changes in the mother, but had no effect on the product of conception. Chlorcyclizine, on the other hand, used as a reference drug in the rat produced fetal malformations at a dose devoid of any toxic activity on the maternal organism. The doses studied in the rabbit were shown to be pharmacologically active in the mothers, producing sedation. No effect, however, was observed on embryofetal development.

A new cephalosporin derivative (ST-21) orally administered in laboratory animals.

The pivaloxymethyl ester of 7-(D-2-amino-2-phenylacetamido)-desacetoxicephalosporanic acid hydrochloride (ST-21) and cephalexin possess the same bacteridal activity. In fact, in the animal body ST-21 releases cephalexin. The acute toxicity study shows the good tolerance of both substances, whereas the tissue distribution is different, both after oral and i.v. administration. Cephalexin concentrations in some tissues of rats and rabbits, particularly in the lungs and kidneys, are higher and longer-lasting in the animals treated with ST-21 than in those receiving cephalexin, thus showing a different pattern of distribution in the body. For this reason ST-21 might be more suited for the treatment of lung and kidney infections.

Influence of phosphoserine on the performance of rats on the rotarod.

The anti-fatigue effect of phosphoserine, L-serine and a mixture of sodium phosphate and L-serine has been studied in rats. Phosphoserine orally administered induced a statistically significant anti-fatigue effect in rats of both sexes submitted to a training test by rotarod, with 14 sessions in 3 days. Furthermore, phosphoserine was utilized better than the mixture of sodium phosphate and L-serine, whereas L-serine alone induced no effect. Therefore the effect of phosphoserine seems to be due to the phosphoryl bond.

Some pharmacological properties of 2-aryl-1,3-indandione derivatives.

Some pharmacological properties of indandione derivatives have been studied in laboratory animals. These substances possess anti-inflammatory, analgesic and anti-coagulent effects, as already known for other indandione derivatives. In addition they possess anti-tussive effects in mice. Unfortunately many of these molecules have also ulcerogenic effects. This fact is disappointing for those indandione derivatives which already are in therapeutic use, as G/18 (Uridion¿) and Emandione¿. It appears that compounds which have two Br in R1 and R4 position possess at the same time low toxicity and no ulcerogenic effects in addition to anti-inflammatory (G/21) and also anti-coagulant (G/22) interesting activity.