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.
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Atkinson RC, Shiffrin RM (1971) The control of short-term memory. Sci Am 224: 82–90
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
Clarke PRF, Eccersley PS, Frisby JP, Thornton JA (1970) The amnesic effect of diazepam ( Valium ). Br J Anaesth 42: 690–697
Curran HV (1986) Tranquillising memories: A review of the effects of benzodiazepines on human memory. Biol Psychol 23: 179–213
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
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
Doenicke A, Ott H (1980) Lormetazepam. Anaesthesiology and Intensivmedizin: 133
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
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
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 )
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
Drachman DA, Leavitt J (1974) Human memory and the cholinergic system. Arch Neurol 30: 113–121
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
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
Dundee JW, George DA (1976) The amnesic action of diazepam, flunitrazepam and lorazepam in man. Acta Anaesth Belg 27: 3–11
File SE, Pellow SS (1986) Intrinsic actions of the benzodiazepine receptor antagonist Ro 151788. Psychopharmacology 88: 1–11
Ghoneim MM, Mewaldt SP (1975) Effects of diazepam and scopolamine on storage, retrieval and organizational process in memory. Psychopharmacology 44: 257–262
Haefely W (1985) Pharmacology of benzodiazepine antagonists. Pharmacopsychiatry 18: 163166
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
Hinrichs JV, Ghoneim MM, Mewaldt SP (1984) Diazepam and memory: retrograde facilitation produced by interference reduction. Psychopharmacology 84: 158–162
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
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
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
Lister RG (1985) The amnesic action of benzodiazepines in man. Neurosci Biobehav Rev 9: 87–94
Lukas SE, Griffiths RR (1982) Precipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15–1788) after 7 days of diazepam. Science 217: 1161–1164
Mann RE, Cho-Young J, Vogel-Sprott M (1984) Retrograde enhancement by alcohol of delayed free recall performance. Pharmacol Biochem Behav 20: 639–642
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
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
Parker ES, Birnbaum IM, Weingartner H, Hartley JT, Stillman RC, Wyatt RJ (1980) Retrograde enhancement of human memory with alcohol. Psychopharmacology 69: 219–222
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
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
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
Stephens DN, Kehr W (1985) ß-Carbolines can enhance or antagonize the effects of punishment in mice. Psychopharmacology 85: 143–147
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
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
Subhan Z, Hindmarch I (1984) Assessing residual effects of benzodiazepines on short term memory. Pharmaceut Med 1: 27–32
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
Tallman JF, Paul SM, Skolnick P, Gallager DW (1980) Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science 207: 274–281
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
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
Weingartner H (1985) Models of memory dysfunction. Ann NY Acad Sci 444: 359–369
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
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights 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