Clinical-pharmacological study with the two isomers (d-, l-) of fenfluramine and its comparison with chlorpromazine and d-amphetamine: psychometric and psychophysiological evaluation.
In a double-blind, placebo-controlled, crossover study, the single oral dose effects of 15, 30 mg d- and 30 mg l-fenfluramine (FEN) on psychometric and psychophysiological variables were investigated and compared with those of 50 mg chlorpromazine (CPZ) and 20 mg d-amphetamine (AMPH). Eighteen healthy young volunteers randomly (latin square) received at weekly intervals the 6 different treatments. Noopsychic, thymopsychic, psychophysiological and flexibility evaluations were carried out at 0, 2, 4, 6 and 8 h after drug administration. Either dose of d- or l-FEN induced only minimal noopsychic and thymopsychic changes. In contrast, 50 mg CPZ produced highly significant deterioration in attention, concentration, reaction time, psychomotor activity and complex reaction, as well as subjective deactivation, while 20 mg d-AMPH produced subjective activation. Critical flicker frequency was only decreased by 50 mg CPZ and increased by 20 mg d-AMPH. In regard to pupillary measurements, 15, 30 mg d-, 30 mg l-FEN and 20 mg d-AMPH produced opposite 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 from the 2nd until the 8th h, followed by 20 mg d-AMPH inducing significant changes from the 4th until the 8th h, but with opposite signs, while FEN treatments exerted only slight effects between the 2nd to 8th h postdrug.
Grünberger
J
J
Section of Pharmacopsychiatry, University of Vienna, Austria.
Saletu
B
B
Linzmayer
L
L
Barbanoj
M J
MJ
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology; D001519:Behavior / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000502:physiology; D011594:Psychometrics; D011597:Psychomotor Performance / Q000187:drug effects*; D011619:Psychotropic Drugs / Q000494:pharmacology; D013237:Stereoisomerism; D013950:Thymus Gland / Q000502:physiology
D011619:Psychotropic Drugs; D005277:Fenfluramine; D000661:Amphetamine; D002746:Chlorpromazine