CLINICAL-PHARMACOLOGICAL STUDY WITH THE 2 ISOMERS (D-FENFLURAMINE, L-FENFLURAMINE) OF FENFLURAMINE AND ITS COMPARISON WITH CHLORPROMAZINE AND D-AMPHETAMINE - PSYCHOMETRIC AND PSYCHOPHYSIOLOGICAL EVALUATION

In a double-blind, placebo-controlled, crossover study, the single ora l dose effects of 15, 30 mg d- and 30 mg l-fenfluramine (FEN) on psych ometric and psychophysiological variables were investigated and compar ed with those of 50 mg chlorpromazine (CPZ) and 20 mg d-amphetamine (A MPH). Eighteen healthy young volunteers randomly (latin square) receiv ed at weekly intervals the 6 different treatments. Noopsychic, thymops ychic, psychophysiological and flexibility evaluations were carried ou t at 0, 2, 4, 6 and 8 h after drug administration. Either dose of d- o r l-FEN induced only minimal noopsychic and thymopsychic changes. In c ontrast, 50 mg CPZ produced highly significant deterioration in attent ion, concentration, reaction time, psychomotor activity and complex re action, as well as subjective deactivation, while 20 mg d-AMPH produce d subjective activation. Critical flicker frequency was only decreased by 50 mg CPZ and increased by 20 mg d-AMPH. In regard to pupillary me asurements, 15,30 mg d-, 30 mg l-FEN and 20 mg d-AMPH produced opposit e changes (widening of pupillary diameter) to those observed after 50 mg CPZ (narrowing of pupil size). Flexibility remained unchanged after FEN treatments, while it consistently decreased after both 50 mg CPZ and 20 mg d-AMPH. Time- and dose/treatment efficacy relations based on discriminant analysis (centroids) of changes in all variables showed 50 mg CPZ as the most psychoactive drug inducing significant changes f rom the 2nd until the 8th h, followed by 20 mg d-AMPH inducing signifi cant changes from the 4th until the 8th h, but with opposite signs, wh ile FEN treatments exerted only slight effects between the 2nd to 8th h postdrug.