Skip to main content
Log in

Comparison of the spectrum of cognitive effects of alprazolam and adinazolam after single doses in healthy subjects

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Single doses of alprazolam (0, 0.5, 1.5 mg) or adinazolam mesylate sustained release tablets (SR) (0, 15, 45 mg) were administered to separate groups of 12 healthy men in a crossover design. Psychomotor performance was assessed by digit symbol substitution (DSST), and memory was assessed using a test battery which reflects various aspects of memory, including attention/working memory, explicit memory (recall of categorically related words), semantic memory (fragmented picture recognition, generation of category exemplars), and implicit memory (time saved in resolving fragmented pictures on the second exposure). Maximal psychomotor performance and memory decrements for the highest active doses were significantly different from placebo for all tasks at some time after dosing. The maximum decrement in DSST was not significantly different between drugs at the high dose (P=0.288). Maximum attention/working memory decrements were significantly different between the high doses of the active compounds (P=0.031), and the difference in maximum category recall decrement was marginally significant (P=0.067). Access to knowledge memory was not significantly altered by these drugs; these results are similar to those obtained for other benzodiazepines. Both drugs exhibited slight effects on implicit memory. The results suggest that the sedative and memory effects of these triazolobenzodiazepines may not be closely related and suggest that adinazolam has a somewhat different spectrum of cognitive effects relative to alprazolam.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barbee JG, Black FW, Kehoe CE, Todorov AA (1991) A comparison of the single-dose effects of alprazolam, buspirone, and placebo upon memory function. J Clin Psychopharmacol 11:351–356

    Google Scholar 

  • Carter CS, Fawcett J, Hertzman M, Papp LA, Jones W, Patterson WM, Swinson RP, Weise CC, Maddock RJ, Sheridan AQ, Liebowitz M (1995) Adinazolam SR in panic disorder with agoraphobia: relationship of daily dose to efficacy. J Clin Psychiatry (in press)

  • Curran HV (1986) Tranquilizing memories: a review of the effects of benzodiazepines on human memory. Biol Psychol 23:179–213

    Google Scholar 

  • Danion JM, Zimmerman MA, Willard-Schroeder D, Grangé D, Singer L (1989) Diazepam induces a dissociation between explicit and implicit memory. Psychopharmacology 99:238–243

    Google Scholar 

  • Danion JM, Peretti S, Grangé D, Bilik M, Imbs JL, Singer L (1992) Effects of chlorpromazine and lorazepam on explicit memory, repetition priming and cognitive skill learning in healthy volunteers. Psychopharmacology 108:345–351

    Google Scholar 

  • Fang JC, Hinrichs JC, Ghoneim MM (1987) Diazepam and memory: evidence for spared memory function. Pharmacol Biochem Behav 28:347–352

    Google Scholar 

  • Fleishaker JC, Phillips JP (1989) Adinazolam pharmacokinetics and behavioral effects following administration of 20–60 mg oral doses of its mesylate salt in healthy volunteers. Psychopharmacology 99:34–39

    Google Scholar 

  • Fleishaker JC, Wright CE (1992) Pharmacokinetic and pharmacodynamic comparison of immediate release and sustained release adinazolam mesylate tablets after single and multiple dose administration. Pharm Res 9:457–463

    Google Scholar 

  • Fleishaker JC, Phillips JP, Smith TC, Smith RB (1989) Multiple dose pharmacokinetics and pharmacodynamics in elderly subjects. Pharm Res 6:379–386

    Google Scholar 

  • Fleishaker JC, Smith TC, Friedman H, Phillips JP (1991)N-desmethyladinazolam pharmacokinetics and behavioral effects following administration of 10–50 mg oral doses in healthy volunteers. Psychopharmacology 105:181–185

    Google Scholar 

  • Fleishaker JC, Sisson TA, Sramek JJ, Conrad J, Veroff AE, Cutler NR (1993) Psychomotor and memory effects of two adinazolam formulations assessed by a computerized neuropsychological test battery. J Clin Pharmacol 33:463–469

    Google Scholar 

  • Funderburk FR, Mackenzie A, Felch L, Bigelow GE, Liebson IA, Griffiths RR (1993) Behavioral evaluation of drugs: a comparison of the behavioral effects of adinazolam and lorazepam. J Clin Res Drug Dev 7:65–75

    Google Scholar 

  • George KA, Dundee JW (1977) Relative amnestic actions of diazepam, flunitrazepam, and lorazepam in man. Br J Clin Pharmacol 4:45–50

    Google Scholar 

  • Ghoneim MM, Mewaldt SP, Berie JL, Hinrichs JV (1981) Memory and performance effects of single and 3-week administration of diazepam. Psychopharmacology 73:147–151

    Google Scholar 

  • Ghoneim MM, Block RI, Ping STS, El-Zahaby, HM, Hinrichs JV (1993) The interactions of midazolam and flumazenil on human memory and cognition. Anesthesiology 79:1183–1192

    Google Scholar 

  • Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcell Dekker, New York

    Google Scholar 

  • Greenblatt DJ, Harmatz JS, Dorsey C, Shader RI (1988) Comparative single-dose kinetics and dynamics of lorazepam, alprazolam, prazepam, and placebo. Clin Pharmacol Ther 44:326–334

    Google Scholar 

  • Hommer D, Weingartner H, Breier A (1993) Dissociation of benzodiazepine-induced amnesia from sedation by flumazenil pretreatment. Psychopharmacology 112:455–460

    Google Scholar 

  • Kroboth PD, Smith RB, Erb RJ (1988) Tolerance to alprazolam after intravenous bolus and continuous infusion: psychomotor and EEG effects. Clin Pharmacol Ther 43:270–277

    Google Scholar 

  • Lister RG (1985) The amnestic action of benzodiazepines in man. Neurosci Biobehav Rev 9:87–94

    Google Scholar 

  • Lister RG, Weingartner H (1987) Neuropharmacological strategies for understanding psychobiological determinants of cognition. Hum Neurobiology 6:119–127

    Google Scholar 

  • Lister R, Weingartner (1991) Perspectives on cognitive neuroscience, Oxford University Press, New York, Oxford

    Google Scholar 

  • Lydiard RB, Lesser IM, Ballenger JC, Rubin RT, Laraia M, DuPont R (1992) A fixed-dose study of alprazolam 2 mg, alprazolam 6 mg, and placebo in panic disorder. J Clin Psychopharmacol 12:96–103

    Google Scholar 

  • Posner M (1989) The foundations of cognitive neuroscience. MIT Press, Cambridge

    Google Scholar 

  • Richardson-Klavelin A, Bjork RA (1988) Measures of memory. Annu Rev Psychol 39:475–543

    Google Scholar 

  • Roth T, Hartse KM, Saab PG, Piccione PM, Kramer M (1980) The effects of flurazepam, lorazepam, and triazolam on sleep and memory. Psychopharmacology 70:231–237

    Google Scholar 

  • Schacter DL (1992) Understanding implicit memory: a cognitive neuroscience approach. Am Psychol 47:559–569

    Google Scholar 

  • Sellal F, Danion JM, Kauffmann-Muller F, Grangé D, Imbs JL, van der Linden M, Singer L (1992) Differential effects of diazepam and lorazepam on repetition priming in healthy volunteers. Psychopharmacology 108:371–379

    Google Scholar 

  • Smith RB, Kroboth PD (1987) Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology 93:105–112

    Google Scholar 

  • Smith RB, Kroboth PD, Vanderlugt JT, Phillips JP, Juhl RP (1984) Pharmacokinetics and pharmacodynamics of alprazolam after oral and IV administration. Psychopharmacology 84:452–456

    Google Scholar 

  • Squire LR, Zola MS (1988) Memory: brain systems and behavior. Special issue: learning and memory. Trends Neurosci 11:170–175

    Google Scholar 

  • Tulving E (1987) Multiple memory systems and consciousness. Human Neurobiology 6:67–80

    Google Scholar 

  • Tulving E, Schacter DL (1990) Priming and human memory systems. Science 247:301–306

    Google Scholar 

  • Wechsler D (1955) A manual for the Wechsler Adult Intelligence Scale. Psychological Corporation, New York

    Google Scholar 

  • Weingartner H, Grafman J, Boutelle W, Kaye W, Martin PR (1983) Forms of memory failure. Science 221[4068]:380–382

    Google Scholar 

  • Weingartner HJ, Hommer D, Lister RG, Thompson K, Wolkowitz O (1992) Selective effects of triazolam on memory. Psychopharmacology 106:341–345

    Google Scholar 

  • Wright CE, Greenblatt DJ, Sisson TA, Scavone JM, Lockniskar A (1994) Steady-state plasma alprazolam concentrations: relationship to psychomotor performance and EEG. Clin Pharmacol Ther 55:142 (abstract)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fleishaker, J.C., Garzone, P.D., Chambers, J.H. et al. Comparison of the spectrum of cognitive effects of alprazolam and adinazolam after single doses in healthy subjects. Psychopharmacology 120, 169–176 (1995). https://doi.org/10.1007/BF02246190

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246190

Key words

Navigation