Alterations in pharmacodynamics of anxiolytics in abstinent alcoholic men: subjective responses, abuse liability, and electroencephalographic effects of alprazolam, diazepam, and buspirone.
Subjective responses, including those associated with abuse liability and changes in frontal electroencephalographic activity, were assessed in abstinent alcoholic men and control subjects after administration of alprazolam, diazepam, buspirone, and placebo. Plasma concentrations of alprazolam, diazepam, and desmethyldiazepam also were determined. Abuse liability scales were elevated for alcoholic participants above control levels after alprazolam and diazepam. Areas under the concentration-time curve differed only for desmethyldiazepam, which was lower for the alcoholic participants. Compared with control subjects, alcoholic participants had greater declines in the absolute power of the alpha band after diazepam challenge. Alcoholic participants, unlike control subjects, had areas under the effect-time curve for alpha and theta bands that were lower after administration of alprazolam or diazepam than they were after receiving placebo. These results suggest that alprazolam and diazepam are more likely to be abused by alcoholic men than by nonalcoholic men and that alcoholic men have enhanced sensitivity to the effects of benzodiazepines on alpha and theta activity.
Ciraulo
D A
DA
National Institute on Drug Abuse/Veterans Affairs Medication Development Research Unit, Boston Veterans Affairs Medical Center, Massachusetts, USA.
Barnhill
J G
JG
Ciraulo
A M
AM
Sarid-Segal
O
O
Knapp
C
C
Greenblatt
D J
DJ
Shader
R I
RI
D000328:Adult; D000339:Affect / Q000187:drug effects; D000437:Alcoholism / Q000378:metabolism* / Q000503:physiopathology; D000525:Alprazolam / Q000493:pharmacokinetics; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D002065:Buspirone / Q000493:pharmacokinetics; D003975:Diazepam / Q000493:pharmacokinetics; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D008297:Male; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000503:physiopathology
D014151:Anti-Anxiety Agents; D003975:Diazepam; D002065:Buspirone; D000525:Alprazolam