Skip to main content
SpringerLink
Log in

Benzodiazepine Receptor Ligands: Tools for Memory Research in Clinical Pharmacology

  • Conference paper
Benzodiazepine Receptor Ligands, Memory and Information Processing

Part of the book series: Psychopharmacology Series ((PSYCHOPHARM,volume 6))

Abstract

In order to study the time course of amnesic effects of the benzodiazepine hypnotic lormetazepam, and their reversal by the benzodiazepine antagonist Ro 15–1788, a combined visual and auditory memory test was developed, which was designed to allow repeated assessments.

Immediate recall as well as delayed free recall and recognition (1 h after drug) were investigated before and after intravenous lormetazepam (0.02 mg/kg) followed 15 min later by intravenous Ro 15–1788 (0.03 mg/kg) or placebo. A third group received placebo followed by Ro 15–1788. Results are based on ten subjects per treatment group and are compared with an age-matched control population (n = 20) without treatment Immediate and delayed recall as well as recognition in both visual and auditory tests were impaired abruptly after intravenous lormetazepam. These effects were reversed instantaneously after Ro 15–1788, which had no marked effect on these parameters when given alone. Ratings by visual analog scales (1 h after drug administration) indicated concomitant sedation and impaired concentration after lormetazepam, which was attenuated by 15–1788. By itself, Ro 15–1788 had no effect on these measures.

Interestingly, the performance in delayed free recall of the visual memory test was significantly enhanced in the lormetazepam group prior to administration. Our results suggest that impaired acquisition of new information after lormetazepam is benzodiazepine receptor mediated and may be associated with a drug-induced enhancement of retrieval of information acquired before lormetazepam administration.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Atkinson RC, Shiffrin RM (1971) The control of short-term memory. Sci Am 224: 82–90

    Article  Google Scholar 

  • Bonetti EP, Pieri L, Cumin R, Schaffner R, Pieri E, Gamzu R, Muller RKM, Haefely WW (1982) Benzodiazepine antagonist Ro 15–1788: neurological and behavioral effects. Psychopharma-cology 78: 8–18

    Article  CAS  Google Scholar 

  • Clarke PRF, Eccersley PS, Frisby JP, Thornton JA (1970) The amnesic effect of diazepam ( Valium ). Br J Anaesth 42: 690–697

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Darragh A, Scully M, O’Boyle C, Brick I, Downie WW (1981) Investigation in man of the efficacy of a benzodiazepine antagonist, Ro 15–1788. Lancet: 8–10

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Doenicke A, Ott H (1980) Lormetazepam. Anaesthesiology and Intensivmedizin: 133

    Google Scholar 

  • Dorow R, Duka T (1986) Anxiety: its generation by drugs and by their withdrawal. In: Biggio G, Costa E (eds) GABAergic transmission and anxiety. Raven, New York, pp 211–225

    Google Scholar 

  • Dorow R, Horowski R, Paschelke G, Amin M, Braestrup C (1983) Severe anxiety induced by FG 7142, a ß-carboline ligand for benzodiazepine receptors. Lancet 11: 98–99

    Article  Google Scholar 

  • Dorow R, Duka T, Sauerbrey N, Höller L ( 1987 a) ß-Carbolines: new insights into the clinical pharmacology of benzodiazepine receptor ligands. In: Dahl S, Gram LF, Paul SM, Potter WZ (eds) Clinical pharmacology in psychiatry: selectivity in psychotropic drug action — promises or problems. Springer, Berlin Heidelberg New York (Psychopharmacology suppl 3 )

    Google Scholar 

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

    Google Scholar 

  • Drachman DA, Leavitt J (1974) Human memory and the cholinergic system. Arch Neurol 30: 113–121

    PubMed  CAS  Google Scholar 

  • Duka T, Ackenheil M, Noderer J, Doenicke A, Dorow R (1986 a) Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15–1788. Psychopharmacology 90: 351–357

    Google Scholar 

  • Duka T, Höller L, Obeng-Gyan R, Dorow R (1986 b) Initial human pharmacology of the neutral benzodiazepine receptor antagonist ß-carboline ZK 93426. Br J Clin Pharmacol 22: 228 P

    Google Scholar 

  • Dundee JW, George DA (1976) The amnesic action of diazepam, flunitrazepam and lorazepam in man. Acta Anaesth Belg 27: 3–11

    PubMed  Google Scholar 

  • File SE, Pellow SS (1986) Intrinsic actions of the benzodiazepine receptor antagonist Ro 151788. Psychopharmacology 88: 1–11

    Article  PubMed  CAS  Google Scholar 

  • Ghoneim MM, Mewaldt SP (1975) Effects of diazepam and scopolamine on storage, retrieval and organizational process in memory. Psychopharmacology 44: 257–262

    Article  CAS  Google Scholar 

  • Haefely W (1985) Pharmacology of benzodiazepine antagonists. Pharmacopsychiatry 18: 163166

    Google Scholar 

  • Higgitt A, Lacer M, Fonagy P (1986) The effects of the benzodiazepine antagonist Ro 15–1788 on psychophysiological performance and subjective measures in normal subjects. Psycho-pharmacology 89: 395–403

    CAS  Google Scholar 

  • Hinrichs JV, Ghoneim MM, Mewaldt SP (1984) Diazepam and memory: retrograde facilitation produced by interference reduction. Psychopharmacology 84: 158–162

    Article  PubMed  CAS  Google Scholar 

  • Hommer DW, Breier A, Paul SM, Davis M, Weingartner H (1986) Ro 15–1788, a specific benzodiazepine antagonist, blocks the sedative, anxiolytic and attentional but not amnestic effects of diazepam in humans (abstr). 25th ACNP Annual Meeting, p 204

    Google Scholar 

  • Hunkeler W, Möhler H, Pieri L, Pole P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290: 514–516

    Article  PubMed  CAS  Google Scholar 

  • Kubicki St, Rohloff A, Ott H, Fichte K (1986) Vigilanz and Amnesie nach Benzodiazepingabe: Neurophysiologische and pharmakopsychologische Aspekte. In: Schulte am Esch J (ed) Benzodiazepine in Anästhesie and Intensivmedizin. Roche, Basel

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Lukas SE, Griffiths RR (1982) Precipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15–1788) after 7 days of diazepam. Science 217: 1161–1164

    Article  PubMed  CAS  Google Scholar 

  • Mann RE, Cho-Young J, Vogel-Sprott M (1984) Retrograde enhancement by alcohol of delayed free recall performance. Pharmacol Biochem Behav 20: 639–642

    Article  PubMed  CAS  Google Scholar 

  • O’Boyle C, Lambe R, Darragh A, Taffe W, Brick I, Kenny M (1983) Ro 15–1788 antagonizes the effects of diazepam in man without affecting its bioavailability. Br J Anaesth 55: 349–356

    Article  PubMed  Google Scholar 

  • Ott H, Hemmerling KG, Kugler J, Suttmann H, Doenicke A, Tesch C, SträBner G (1980) Amnestische Begleitwirkungen nach i. v.-Gabe von Lormetazepam and Flunitrazepam. In: Doe-nicke A, Ott H (eds) Lormetazepam Noctamid. Springer, Berlin Heidelberg New York, pp 13.1–13. 10

    Google Scholar 

  • Parker ES, Birnbaum IM, Weingartner H, Hartley JT, Stillman RC, Wyatt RJ (1980) Retrograde enhancement of human memory with alcohol. Psychopharmacology 69: 219–222

    Article  PubMed  CAS  Google Scholar 

  • Parker ES, Morihisa JM, Wyatt RJ, Schwartz BL, Weingartner H, Stillman RC (1981) The al- cohol facilitation effect on memory: a dose-response study. Psychopharmacology 74: 88–92

    Article  PubMed  CAS  Google Scholar 

  • Roehrs T, McLenaghan A, Koshorek G, Zorick F, Roth T (1984) Amnesic effects of lormetazepam. In: Hindmarch I, Ott H, Roth T (eds) Sleep, benzodiazepines and performance. Springer, Berlin Heidelberg New York, pp 165–172

    Google Scholar 

  • Schöpf J, Laurian S, Le PK, Gaillard J-M (1984) Intrinsic activity of the benzodiazepine antagonist Ro 15–1788 in man: an electrophysiological investigation. Pharmacopsychiatry 17: 79–83

    Article  PubMed  Google Scholar 

  • Stephens DN, Kehr W (1985) ß-Carbolines can enhance or antagonize the effects of punishment in mice. Psychopharmacology 85: 143–147

    Article  PubMed  CAS  Google Scholar 

  • Study RE, Barker JL (1981) Diazepam and (—)pentobarbital. Fluctuation analysis reveals different mechanisms for potentiation of GABA responses in cultured central neurons. Proc Natl Acad Sci USA 78: 7180–7184

    Google Scholar 

  • Subhan Z (1984) The effects of benzodiazepines on short-term memory and information processing. In: Hindmarch I, Ott H, Roth T (eds) Sleep, benzodiazepines and performance. Springer, Berlin Heidelberg New York Tokyo, pp 173–181

    Google Scholar 

  • Subhan Z, Hindmarch I (1984) Assessing residual effects of benzodiazepines on short term memory. Pharmaceut Med 1: 27–32

    CAS  Google Scholar 

  • Sunderland T, Tariot PN, Weingartner H, Murphy DL, Newhouse PA, Mueller EA, Cohen RM (1986) Pharmacological modelling of Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 10: 599–610

    Article  PubMed  CAS  Google Scholar 

  • Tallman JF, Paul SM, Skolnick P, Gallager DW (1980) Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science 207: 274–281

    Article  PubMed  CAS  Google Scholar 

  • Thiebot M-H, Childs M, Soubrie P, Simon P (1983) Diazepam induced release of behavior in an extinction procedure: Its reversal by Ro 15–1788. Eur J Pharmacol 88: 111–116

    Article  PubMed  CAS  Google Scholar 

  • Venault P, Chapoutier G, de Carvalho LP, Simiand J, Morre M, Dodd RH, Rossier J (1986) Benzodiazepine impairs and ß-carboline enhances performance in learning and memory. Nature 321: 864–866

    CAS  Google Scholar 

  • Weingartner H (1985) Models of memory dysfunction. Ann NY Acad Sci 444: 359–369

    Article  PubMed  CAS  Google Scholar 

  • Wolkowitz OM, Weingartner H, Thompson K, Pickar D, Paul SM, Hommer DW (1987) Diazepam-induced amnesia: a neuropharmacological model of an “organic amnestic syndrome”. Am J Psychiatry 144: 25–29

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, St. Vinzenz Krankenhaus, Altena, Germany

    D. Berenberg

  2. Research Laboratories, Department of Clinical Neuropsychopharmacology, Schering AG, 1000, Berlin 65, Germany

    R. Dorow, T. Duka & N. Sauerbrey

Authors
  1. D. Berenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Dorow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Duka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. Sauerbrey
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Human Psychopharmacology Research Unit, University of Leeds, LS2 9JT, Leeds, UK

    Ian Hindmarch (Head) (Head)

  2. Research Laboratories Department Pharmacopsychology, Schering AG, P. O. Box 65 03 11, 1000, Berlin 65, Federal Republic of Germany

    Helmut Ott

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Berenberg, D., Dorow, R., Duka, T., Sauerbrey, N. (1988). Benzodiazepine Receptor Ligands: Tools for Memory Research in Clinical Pharmacology. In: Hindmarch, I., Ott, H. (eds) Benzodiazepine Receptor Ligands, Memory and Information Processing. Psychopharmacology Series, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73288-1_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73288-1_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73290-4

  • Online ISBN: 978-3-642-73288-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation