Hostname: page-component-55f67697df-2mk96 Total loading time: 0 Render date: 2025-05-11T09:45:21.822Z Has data issue: false hasContentIssue false
  • English
  • Français

Central Actions of Benzodiazepines: General Introduction

Published online by Cambridge University Press:  29 January 2018

W. E. Haefely
W. E. Haefely*
Affiliation:
Pharma Research Department, Building 69, F. Hoffmann–La Roche & Co. Ltd., CH 4002 Basle, Switzerland
Get access Rights & Permissions [Opens in a new window]

Summary

After a brief review of the characteristic somatic and psychotropic effects of benzodiazepines evidence is presented which supports a specific facilitatory action of these drugs on GABA ergic synapses within the mammalian central nervous system. Benzodiazepines enhance presynaptic inhibition in the spinal cord and dorsal column nuclei as well as postsynaptic inhibition in dorsal column nuclei, hippocampus, hypothalamus, cerebral cortex, cerebellar cortex, which are all examples of recurrent and collateral inhibition mediated by GABA ergic intrinsic neurones. In addition, the compounds also enhance the inhibitory effect of GABA ergic long projection neurones in the substantia nigra and the lateral vestibular nucleus of Deiters. Several problems remain to be solved, such as the exact site at which benzodiazepines initiate their action (pre-synaptically at GABA ergic nerve endings or postsynaptically at the target cells) and the possible existence of endogenous ligands for the benzodiazepine receptor. Some suspected implications which studies on benzodiazepine binding sites could have for a deeper understanding of the mode of action of these drugs are discussed.

Type
Symposium
Information
The British Journal of Psychiatry , Volume 133 , Issue 3 , September 1978 , pp. 231 - 238
Copyright
Copyright © Royal College of Psychiatrists, 1978 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Bowery, N. G. & Dray, A. (1978) Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs. British Journal of Pharmacology, 63, 197–215.Google Scholar
Choi, D. W., Farb, D. H. & Fischbach, G. D. (1977) Chlordiazepoxide selectively augments GABA action in spinal cord cell cultures. Nature, 269, 342–4.Google Scholar
Chou, D. T. & Wang, S. C. (1977) Unit activity of amygdala and hippocampal neurons: effects of morphine and benzodiazepines. Brain Research, 126, 427–40.CrossRefGoogle ScholarPubMed
Cook, L. & Davidson, A. B. (1973) In The Benzodiazepines (eds Garattini, S., Mussini, E., Randall, L. O.). New York: Raven Press, pp 327–45.Google Scholar
Costa, E. & Greengard, P. (eds.) (1975) Mechanism of action of benzodiazepines. New York: Raven Press.Google ScholarPubMed
Costa, E. Guidotti, A., Mao, C. C. & Suria, A. (1975) New concepts on the mechanism of action of benzodiazepines. Life Sciences, 17, 167–86.Google Scholar
Dantzer, R. (1977) Behavioural effects of benzodiazepines: a review. Biobehavioural Reviews, 1, 71–86.Google Scholar
Geller, H. M., Taylor, D. A. & Hoffer, B. J. (1978) Benzodiazepines and central inhibitory mechanisms. Naunyn-Schmiedeberg's Archives of Pharmacology (in press).Google Scholar
Guidotti, A. (1978) Synaptic mechanisms in the action of benzodiazepines. In Psychopharmacology: A Generation of Progress (eds Lipton, M. A., Di Mascio, A., Killam, K. F.). New York: Raven Press, pp 1349–57.Google Scholar
Haefely, W. E. (1977) Synaptic pharmacology of barbiturates and benzodiazepines. Agents and Actions, 7, 353–9.Google Scholar
Haefely, W. E. (1978) Behavioral and neuropharmacological aspects of drugs used in anxiety and related states. In Psychopharmacology: A Generation of Progress (eds Lipton, M. A., Di Mascio, A., Killam, K. F.). New York: Raven Press, pp 1359–74.Google Scholar
Haefely, W. E. Keller, H. H., Pieri, L., Polc, P., Schaffner, R. & Zihlmann, R. (1978 in press) Interaction of minor tranquillizers with synaptic processes mediated by GABA. Proceedings of the 10th C.I.N.P. Congress. Oxford: Pergamon Press Ltd.Google Scholar
Haefely, W. E. Kulcsár, A., Möhler, H., Pieri, L., Polc, P. & Schaffner, R. (1975) Possible involvement of GABA in the central actions of benzodiazepines. In Mechanism of Action of Benzodiazepines (eds Costa, E., Greengard, P.). New York: Raven Press, pp 131–51.Google Scholar
Jalfre, M., Monachon, M.-A. & Haefely, W. (1971) Effects on the amygdalo-hippocampal evoked potential in the cat of four benzodiazepines and some other psychotropic drugs. Naunyn-Schmiedeberg's Archives of Pharmacology, 270, 180–91.Google Scholar
Keller, H. H., Schaffner, R. & Haefely, W. (1976) Interaction of benzodiazepines with neuroleptics at central dopamine neurons. Naunyn-Schmiedeberg's Archives of Pharmacology, 294, 1–7.Google Scholar
Kozhechkin, S. N. & Ostrovskaya, R. U. (1977) Are benzodiazepines GABA antagonists? Nature, 260, 72–3.Google Scholar
Levy, R. A. (1977) The role of GABA in primary afferent depolarization. Progress in Neurobiology, 9, 211–67.Google Scholar
MacDonald, R. & Barker, J. L. (1978) Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones. Nature, 271, 563–4.Google Scholar
Nicoll, R. (1978) Selective actions of barbiturates on synaptic transmission. In Psychopharmacology: A Generation of Progress (eds Lipton, M. A., Di Mascio, A., Killam, K. F.). New York: Raven Press, pp 1337–48.Google Scholar
Olsen, R. W., Ticku, M. K., Van Ness, P. C. & Greenlee, D. (1978) Effects of drugs on γ-aminobutyric acid receptors, uptake, release and synthesis in vitro. Brain Research, 139, 277–94.Google Scholar
Pieri, L. & Haefely, W. (1976) The effect of diphenylhydantoin, diazepam and clonazepam on the activity of Purkinje cells in the rat cerebellum. Naunyn-Schmiedeberg's Archives of Pharmacology, 296, 1–4.Google Scholar
Polc, P. & Haefely, W. (1975) Effects of flunitrazepam on the sleep of cats. In Sleep 1974 (eds Levin, P., Koella, W. P.). Basel: S. Karger AG, pp 303–5.Google Scholar
Polc, P. & Haefely, W. (1976) Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus. Naunyn-Schmiedeberg's Archives of Pharmacology, 294, 121–31.Google Scholar
Polc, P. & Haefely, W. (1977) Effects of systemic muscimol and GABA in the spinal cord and superior cervical ganglion of the cat. Experientia, 33, 809.Google Scholar
Polc, P. Möhler, H. & Haefely, W. (1974) The effect of diazepam on spinal cord activities: possible sites and mechanisms of action. Naunyn-Schmiedeberg's Archives of Pharmacology, 284, 319–37.Google Scholar
Raabe, W. & Gumnit, R. J. (1977) Anticonvulsant action of diazepam: increase of cortical postsynaptic inhibition. Epilepsia, 18, 117–20.Google Scholar
Schaffner, R. & Haefely, W. (1975) The effects of diazepam and bicuculline on the strio-nigral evoked potential. Experientia, 31, 732.Google Scholar
Schallek, W., Schlosser, W. & Randall, L. O. (1972) Recent developments in the pharmacology of the benzodiazepines. Advances in Pharmacology and Chemotherapy, 10, 119–83.Google Scholar
Schmidt, R. F., Vogel, E. & Zimmermann, M. (1967) Die Wirkung von Diazepam auf die präsynaptische Hemmung und andere Rückenmarksreflexe. Naunyn-Schmiedeberg's Archives of Pharmacology, 258, 69–82.CrossRefGoogle Scholar
Wolf, P. & Haas, H. L. (1977) Effects of diazepines and barbiturates on hippocampal recurrent inhibition. Naunyn-Schmiedeberg's Archives of Pharmacology, 299, 211–18.Google Scholar
Zakusov, V. V., Ostrovskaya, R. U., Markovitch, V. V., Molodavkin, G. M. & Bulayev, V. M. (1975) Electrophysiological evidence for an inhibitory action of diazepam upon brain cortex. Archives internationales de Pharmacodynamic et de Thérapie, 214, 188–205.Google ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.