Oral D-fenfluramine and neuroendocrine challenge: problems with the 30 mg dose in men

Ten healthy male volunteers of normal weight received 30 mg of D-fenfluramine, a putative selective releaser of 5-hydroxytryptamine (5-HT), and placebo by mouth in balanced order at a 1 week interval after a light breakfast. Blood was taken for estimation of plasma cortisol and prolactin, and the patients completed self rating scales for stress and arousal and rated themselves on visual analogue scales for mood, hunger and alertness at appropriate time points from 30 min before to 300 min after drug/placebo ingestion. There were no statistically discernible effects of D-fenfluramine on either hormone measures or subjective ratings. The failure to find effects may be due to a too low dose of D-fenfluramine and/or a lower sensitivity to the drug in men compared with women. More information is required on the dose/response relationship and drug absorption especially after food. However, the findings cast doubt on results already obtained employing this dose of the drug in studies that have included male subjects. Furthermore, the interpretation of earlier studies with D,L-fenfluramine at a dose of 60 mg is also made more uncertain by the failure to confirm that the more selective D-isomer produces equivalent effects.