The
gamma-aminobutyric acid (
GABA) agonist alprazolam is known to decrease
adrenocorticotropic hormone and
cortisol concentrations.
Dehydroepiandrosterone (
DHEA) is secreted synchronously with
cortisol by the adrenal glands and demonstrates diurnal variation. The major objective of this study was to determine whether
alprazolam affects concentrations of
DHEA and
DHEA-S, the sulfated metabolite. In vitro studies have demonstrated that
DHEA-S, and perhaps
DHEA, have
GABA antagonistic activity. Another objective was to determine whether
DHEA-S and/or
DHEA concentrations are related to
psychomotor impairment after
alprazolam. Thirty-eight healthy volunteers (25 young men, aged 22-35, and 13 elderly men, aged 65-75) received a single intravenous dose of
alprazolam 2 mg/2 min (part 1). Fifteen young and 13 elderly men responded to
alprazolam and agreed to participate in part 2 of the study, which was a crossover of placebo and
alprazolam infusion to plateau for 9 hours. Plasma samples at 0, 1, 4, and 7 hours were assayed for
steroid concentrations.
Alprazolam produced (1) significant increases in
DHEA concentrations at 7 hours in both young and elderly
men; (2) significant decreases in
cortisol concentrations; and (3) no change in
DHEA-S concentrations. The relationship between psychomotor decrement and
DHEA concentrations at 7 hours after
alprazolam 2 mg/2 min was described by a u-shaped curve (p < 0.0047). Both the linear and quadratic components of the equations for the tests were significant (p < 0.002). These results suggest that
alprazolam modulates peripheral concentrations of
DHEA and that
DHEA and/or
DHEA-S may have an in vivo role in modulating
GABA receptor-mediated responses.