Reduction of normal food intake in rats and dogs and inhibition of experimentally induced hyperphagia in rats by CM 57373 and fenfluramine.

The anorectic effect of CM 57373 in dogs and in rats food-deprived or with experimentally induced hyperphagia (cafeteria-diet hyperphagia and insulin hyperphagia) was compared to the effect of serotoninergic anorectic drug dl-fenfluramine. CM 57373 and dl-fenfluramine administered orally caused a dose-related reduction of food consumption by food-deprived rats (ID50 = 7.4 mg/kg and 2.5 mg/kg respectively). The oral ID50 in dogs was 2.4 mg/kg for CM 57373 and 1.1 mg/kg for dl-fenfluramine. This animal species tolerated CM 57373 better than dl-fenfluramine. The latter induced mydriasis, dyskinesia and reduced spontaneous activity. The anorectic effects of CM 57373 and dl-fenfluramine in cafeteria-diet hyperphagic rats were comparable. Tolerance to the anorectic effect developed in rats treated with both CM 57373 and dl-fenfluramine although tolerance was initially less pronounced with CM 57373 than dl-fenfluramine. The brain serotonin levels of cafeteria-fed rats were unchanged by CM 57373 throughout treatment whereas dl-fenfluramine decreased the monoamine levels starting from the 8th day. Both drugs reduced 5-hydroxyindolacetic acid levels. CM 57373 (7.4 mg/kg p.o.) and dl-fenfluramine (2.5 mg/kg p.o.) markedly reduced the overeating caused by insulin injection. These results indicate that CM 57373 shows several characteristics of drugs that act via serotonin to depress food intake in various animal species.

Haemodynamic effects of the renin inhibitor SR 42128 in conscious baboons.

We studied the haemodynamic effects of captopril [3 mg/kg intravenously (i.v.)] and SR 42128 (8 mg/kg in a 30-min perfusion) in the conscious baboon after sodium depletion by furosemide. The evolution of the following parameters was studied: plasma renin activity (PRA), heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), first derivative of the left intraventricular pressure (dP/dt) and total peripheral resistance (TPR). Captopril (n = 5) increased PRA twofold and decreased MAP and TPR. Heart rate, CO and dP/dtmax were not significantly modified. As compared with a control group (n = 5), SR 42128 (n = 5) decreased PRA to almost undetectable levels for at least 2 h and decreased MAP, CO and TPR. It did not alter HR or dP/dtmax. Thus we can conclude that SR 42128 is a long-acting inhibitor of circulating renin in baboons and, in our experimental conditions, SR 42128, like captopril, induced a decrease in blood pressure without detrimental effect on cardiac function.

[Phototoxicity of Bergamot oil. Comparison between humans and guinea pigs]. / Etude expérimentale de la phototoxicité de l'essence de Bergamote. Corrélations entre l'homme et le cobaye.

Phototoxicity of bergamot oil in solar simulating radiation (SSR greater than or equal to 290 nm) and in long ultraviolet radiation (LUV greater than or equal to 320 nm) has been compared by studying photoaugmentation of erythema in the guinea pig after 24 h and pigmentary photoaugmentation in man on the 8th day. The results show that a close relationship exists between guinea pig and human responses, with both radiations used, and that man seems to be slightly more sensitive to phototoxic effects of bergamot oil than the guinea pig. This difference of sensitivity necessarily implies the participation of UVA (320--400 nm) in the phototoxic reaction of bergamot oil with solar radiation. This UVA participation is particularly obvious in the guinea pig; in man, the results are less clear and a certain synergy of UVB rays (290--320 nm) may be involved in the phototoxic UVA-induced reaction of bergamot oil. Despite these slight differences, the erythematous reaction in the guinea pig appears to be a remarkable experimental model to show out potential phototoxic reactions of products containing psoralens in man.