Skip to main content
Log in

Differentiating the sedative, psychomotor and amnesic effects of benzodiazepines: a study with midazolam and the benzodiazepine antagonist, flumazenil

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

Abstract

Sixteen healthy volunteers were administered midazolam followed by placebo or the benzodiazepine antagonist, flumazenil, in a double-blind, cross-over study. Flumazenil reversed midazolam-induced sedation on the subjective, psychophysiological and motor indices used. In contrast, there was little evidence of any reversal of amnesic effects, which were assessed using both direct (explicit) and indirect (implicit) measures of memory. Results are discussed in terms of dissociating the sedative and amnesic effects of benzodiazepines.

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

  • Birch BRP, Curran HV (1990) The differential effects of flumazenil on the psychomotor and amnesic actions of midazolam. J Psychopharmacol 4:29–34

    Google Scholar 

  • Birch BRP, Anson KM, Gellister J, Parker C, Miller RA (1990) The role of midazolam and flumazenil in urology. Acta Anaes Scand [Suppl. 92] 34:25–32

    Google Scholar 

  • Bond AJ, Lader MH (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218

    Google Scholar 

  • Brown MW, Brown J, Bowes J (1989) Absence of priming coupled with substantially preserved recognition in lorazepam induced amnesia. Q J Exp Psychol 41A:599–617

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Curran HV (1991) Antianxiety treatments and human memory In: Brierly M, File S (eds) New concepts in anxiety. McMillan, London

    Google Scholar 

  • Curran HV, Schiwy W, Lader M (1987) Differential amnesic properties of benzodiazepines: a dose response comparison of two drugs with similar elimination half-lives. Psychopharmacology 92:358–364

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Darragh A, Lambe R, Kenny M, Brick I, Taafe WO, O'Boyle C (1982) Ro 15-1788 antagonises the central effects of diazepam in man without altering diazepam availability. B J Clin Pharmacol 14:677–682

    Google Scholar 

  • Dorow R, Duka T (1986) Anxiety: its generation by drugs and their withdrawal. In: Biggio C, Costa E (eds) GABAergic transmission and anxiety. Raven Press, New York, pp 221–225

    Google Scholar 

  • Dorow R, Berenberg D, Duka T, Sauerberg N (1987) Amnestic effects of lormetazepam and their reversal by the benzodiazepine antagonist Ro 15-1788. Psychopharmacology 93:507–514

    Article  PubMed  Google Scholar 

  • Dunton AW, Schwam E, Pitman V, McGrath J, Hendler J, Siegal J (1988) Flumazenil: US clinical pharmacology studies. Eur J Anaethesiol 52:81–95

    Google Scholar 

  • Eysenck MW (1984) A handbook of cognitive psychology. Lawrence Erlbaum, London

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Frey PW, Colliver JA (1973) Sensitivity and responsivity measures in discrimination learning. Learn Motiv 4:327–342

    Article  Google Scholar 

  • Frith CD (1967) The effects of nicotine on tapping. Life Sci 6:321–326

    Article  PubMed  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

    Article  PubMed  Google Scholar 

  • Graf P, Squire LR, Mandler G (1984) The information that amnesic patients do not forget. J Exp Psychol Learn Mem Cogn 10:164–178

    Article  PubMed  Google Scholar 

  • Haefely W (1985) Tranquillizers. In: Grahame-Smith DG, Cohen PJ (eds) Psychopharmacology 2, Part 1: Preclinical psychopharmacology. Elsevier, Amsterdam

    Google Scholar 

  • Hommer DW, Brier A, Paul SM, Davis M, Weingartner H (1986) Ro 15-1788, a specific benzodiazepine antagonist, blocks the sedative, anxiolytic and attentional but not the amnestic effects of diazepam in humans. Abstracts of the 25th ANCP Annual Meeting, Washington

  • Hunkeller W, Mohler H, Pieri L, Polc P, Bonetti E, Cumin R, Schaffner R, Haefly W (1981) Selective antagonists of the benzodiazepines. Nature 290:574–576

    Google Scholar 

  • Morre M, Bachy A, Keane PC (1985) Differential CNS binding of benzodiazepines. Supplement Actualites Medicales Internationales: Psychiatrie 2:28–32

    Google Scholar 

  • O'Boyle C, Lambe R, Darragh A, Taffe W, Brick I, Kenny M (1983) Ro 15-1788 antagonises the effects of diazepam in man without affecting its bioavailability. Br J Anaesth 35:349–354

    Google Scholar 

  • Ricou B, Forster A, Bruckner P, Chastonay P, Gemperle M (1986) Clinical evaluation of a specific benzodiazepine antagonist (Ro 15-1788). Br J Anaesthesiol 58:1005–1011

    Google Scholar 

  • Rosenbaum NL, Hooper PA (1988) The effects of flumazenil, a new benzodiazepine antagonist, on the reversal of midazolam sedation and amnesia in dental patients. Br Dent J 165:400–402

    Article  PubMed  Google Scholar 

  • Sage DJ, Close A, Boas RA (1987) Reversal of midazolam sedation with anexate. Br J Anaethesiol 59:459–464

    Google Scholar 

  • Tulving E (1972) Episodic and semantic memory. In: Tulving E, Donaldson W (eds) Organisation of memory. Academic Press, New York, pp 381–403

    Google Scholar 

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

    Google Scholar 

  • Wesnes K, Simpson PM, Christmas L (1987) The assessment of human information processing abilities in psychopharmacology. In: Hindmarch I, Stonier PD (eds) Human psychopharmacology: measures and methods, vol 1. Wiley, Chichester, pp 79–92

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Curran, H.V., Birch, B. Differentiating the sedative, psychomotor and amnesic effects of benzodiazepines: a study with midazolam and the benzodiazepine antagonist, flumazenil. Psychopharmacology 103, 519–523 (1991). https://doi.org/10.1007/BF02244252

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244252

Key words

Navigation