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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Birch BRP, Curran HV (1990) The differential effects of flumazenil on the psychomotor and amnesic actions of midazolam. J Psychopharmacol 4:29–34
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
Bond AJ, Lader MH (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218
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
Curran HV (1986) Tranquillising memories: a review of the effects of benzodiazepines on human memory. Biol Psychol 23:179–213
Curran HV (1991) Antianxiety treatments and human memory In: Brierly M, File S (eds) New concepts in anxiety. McMillan, London
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
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
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
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
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
Dunton AW, Schwam E, Pitman V, McGrath J, Hendler J, Siegal J (1988) Flumazenil: US clinical pharmacology studies. Eur J Anaethesiol 52:81–95
Eysenck MW (1984) A handbook of cognitive psychology. Lawrence Erlbaum, London
Fang JC, Hinrichs JV, Ghoneim MM (1987) Diazepam and memory: evidence for spared memory function. Pharmacol Biochem Behav 28:347–352
Frey PW, Colliver JA (1973) Sensitivity and responsivity measures in discrimination learning. Learn Motiv 4:327–342
Frith CD (1967) The effects of nicotine on tapping. Life Sci 6:321–326
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
Graf P, Squire LR, Mandler G (1984) The information that amnesic patients do not forget. J Exp Psychol Learn Mem Cogn 10:164–178
Haefely W (1985) Tranquillizers. In: Grahame-Smith DG, Cohen PJ (eds) Psychopharmacology 2, Part 1: Preclinical psychopharmacology. Elsevier, Amsterdam
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
Morre M, Bachy A, Keane PC (1985) Differential CNS binding of benzodiazepines. Supplement Actualites Medicales Internationales: Psychiatrie 2:28–32
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
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
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
Sage DJ, Close A, Boas RA (1987) Reversal of midazolam sedation with anexate. Br J Anaethesiol 59:459–464
Tulving E (1972) Episodic and semantic memory. In: Tulving E, Donaldson W (eds) Organisation of memory. Academic Press, New York, pp 381–403
Wechsler D (1955) Manual for the Wechsler Adult Intelligence Scale. Psychological Corporation, New York
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
Author information
Authors and Affiliations
Rights 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
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244252