Chronobiometric identification of disorders of hunger sensation in essential obesity: therapeutic effects of dexfenfluramine.

In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride; Servier, Orléans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a "chronoanorectic drug" that interacts with the chronobiologic properties of the serotoninergic system.

[Clinical observations on the treatment of obese patients with dexfenfluramine]. / Osservazioni cliniche sul trattamento di pazienti obesi con dexfenfluramina.

In a 12-months double-blind study 42 obese patients (5 males, 37 females) were treated either with d-fenfluramine (30 mg daily) or with placebo plus low-calorie diet (1500-1200 kcal daily). Evaluation of treatment efficacy was based on evolution of the initial cohort, weight loss, number of subjects completing treatment, tolerability and events leading to dropout. Patients receiving d-fenfluramine had statistically significant greater weight loss than the placebo group; 30 mg daily proved to be an effective and well tolerated dose of d-fenfluramine with the best long-term activity/acceptability ratio.

Ketanserin (S2-receptor blocking agents), hypertension and chronic alcoholism.

Ketanserin is a pure antagonist of serotonin S2-receptors, in blood vessels, platelets and bronchial tissue. Ketanserin has been suggested as hypotensive drug in man, but it shows as well a specific activity on platelet aggregation. An increased incidence of hypertension, of unknown origin, has been found in patients with chronic alcoholism: hypotheses have been made upon an increased incretion of catecholamines and a greater sensitivity of blood vessels' receptors to their action. The data from the present study of eleven patients show that these subjects had an increased platelet activity and ketanserin administration was effective in allowing both the blood pressure levels and platelet activity to resume their normal range. This drug is thus suggested, for its pharmacological properties, as an elective medication for hypertensive patients with chronic alcoholism.

Ketanserin (S2-receptor blocking agent), platelet activity and chronic alcoholism.

Ketanserin is a pure and selective antagonist of serotonin S2-receptors in blood vessels, platelets and bronchial tissue. It antagonizes serotonin-induced vasoconstriction, bronchoconstriction and platelet aggregation, and indirectly it blocks platelet release reaction. Ketanserin has little or no effect on healthy subjects. Serotonin-induced or serotonin-potentiated platelet aggregation is inhibited in blood drawn from ketanserin-treated healthy volunteers. Oral or parenteral ketanserin treatment did not cause major changes in beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) plasma concentrations, when basic values were normal. Increased microaggregate formation was found in alcoholics and heavy drinkers. It was also found that beta-TG and PF4 levels were higher in these patients than in the controls. Ketanserin treatment tended to normalize these protein levels in such patients.