Effects of Fenfluramine and Ritanserin on Prolactin Response to Insulin-Induced Hypoglycemia in Obese Patients: Evidence for Failure of the Serotoninergic System

Abstract

In order to study the hypothesized impairment of the serotoninergic system in human obesity, an insulin tolerance test (ITT) was carried out on 12 obese normoprolactinemic women and on 6 normal-weight women before (A) and after (B) the administration of a serotoninergic drug, fenfluramine (60 mg twice a day per os for 7 days). After a washout period, a new ITT (C) followed the administration of fenfluramine at the same dose, associated with a specific S2 blocker receptor agent, ritanserin (30 mg/day for the first 2 days and 20 mg/day for a further 5 days). In obese subjects, the prolactin (PRL) response to ITT A was reduced as compared to the controls: in 6 patients (‘nonresponders’) the PRL levels did not change, while in the other 6 (‘responders’) they increased (p < 0.003) but less than in the controls (p < 0.02). In normal-weight subjects, the administration of fenfluramine alone or with ritanserin did not modify the PRL response to ITT. In the responders, the serotoninergic drug normalized the PRL response to ITT while significantly improving it in the nonresponders; these effects were not antagonized by ritanserin. In conclusion, our data suggest that the serotoninergic system of obese patients is impaired and that the different secretory pattern observed in the two groups before and after fenfluramine may reflect differing degrees of this impairment.

Impaired Growth Hormone Response to Insulin‐induced Hypoglycaemia in Obese Patients: Restoration Blocked by Ritanserin After Fenfluramine Administration

“…Furthermore, the present results agree with those obtained in human studies showing a normalization of GH response to arginine by FF in obese patients (Altomonte et al, 1987). Finally, they confirm our previous report (Bernini et al, 1989) in which this drug was found to restore PRL responsiveness to IIH in these patients.…”

Increased body weight associated with prolactin secreting pituitary adenomas: weight loss with normalization of prolactin levels

“…On the other hand, healthy obese subjects have decreased prolactin responses to insulin‐induced hypoglycaemia and TRH stimulation (Donders et al ., 1985; Weaver et al ., 1990). Impairment of the serotoninergic (Bernini et al ., 1989; Pijl et al ., 1993) and the opioidergic (Argenio et al ., 1991) pathways have been implicated in this impaired modulation of prolactin release.…”