DO ALPRAZOLAM-INDUCED CHANGES IN SACCADIC EYE-MOVEMENT AND PSYCHOMOTOR FUNCTION FOLLOW THE SAME TIME-COURSE

The purpose of this study was to determine whether short-term toleranc e develops to GABA-agonist-induced changes in saccadic eye movements ( SEMs), and whether the time course for GABA-agonist induced onset and offset of impairment is similar for SEMs and for psychomotor function. An additional goal was to determine whether there are differences in sensitivity between SEMs and psychomotor function. Six healthy volunte ers participated in this balanced double-blind, three-way crossover, s ingle-dose study of placebo and two different dosage forms of the GABA -agonist alprazolam: a rapidly absorbed oral 1.5-mg compressed tablet (CT) and a 3.0-mg sustained release (SR) tablet. Treatments were separ ated by a 7-day washout period. Peak concentrations did not differ bet ween CT and SR treatments, although area under the concentration-time curve (AUC) of alprazolam was greater after administration of SR than after CT, because plateau concentrations were attained after SR. Both SEM and psychomotor tests showed time-dependent responses consistent w ith the development of tolerance. SEMs discriminated the differences i n rate of drug input of the CT and SR formulations, with impairment ev ident at low concentrations during absorption. SEM impairment also per sisted longer than did psychomotor impairment. Peak saccade velocity i s a more sensitive indicator of pharmacologic effects mediated by the GABA-benzodiazepine receptor complex than are psychomotor responses. T his is probably the result of the very high GABA dependency of SEMs, a long with their limited sensitivity to motivation. (C)1998 The America n College of Clinical Pharmacology.