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The Benzodiazepine Receptor in Normal and Pathological Human Brain

Published online by Cambridge University Press:  29 January 2018

H. Möhler  and
T. Okada
H. Möhler*
Affiliation:
Pharmaceutical Research Department, F. Hoffmann-La Roche, Basle, Switzerland; University of Freiburg, Freiburg, West Germany
T. Okada
Affiliation:
Nippon Roche Research Center, Biochemistry Department, 200 Kajiwara, Kamakura City, Japan
*
Correspondence to: Dr H. Möhler.
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Summary

Benzodiazepines bind with high affinity to a specific benzodiazepine receptor, which occurs exclusively in the central nervous system. The affinity of various benzodiazepines to the receptor closely parallels their pharmacological and therapeutic potency. Binding to the receptor is stereospecific. The receptor is mainly localized in the synaptic membrane fraction and has its highest density in cortical areas of the brain. In Huntington's chorea a decrease in benzodiazepine receptor binding is found in caudate nucleus and putamen, which, at least in putamen, is due to a loss of benzodiazepine receptors apparently located on GABA neurones, which degenerate in Huntington's chorea. The loss of benzodiazepine receptors might explain why the ameliorative effects of benzodiazepines in the early stages of the disease are not sustained in the later stages.

Information

Type
Research Article
Information
The British Journal of Psychiatry , Volume 133 , Issue 3 , September 1978 , pp. 261 - 268
Copyright
Copyright © Royal College of Psychiatrists, 1978 

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Footnotes

Presented at the Annual Meeting of the British Association for Psychopharmacology held on 7 April 1978

References

1 Avant, G. R., Klotz, U., Wilkinson, G. R., Hoyampa, A. & Schenker, S. (1974) Altered disposition of diazepam in liver disease. Journal of Clinical Investigation, 53, 2a–3a.Google Scholar
2 Braestrup, C., Albrechtsen, R. & Squires, R. F. (1977) High densities of benzodiazepine receptors in human cortical areas. Mature, 269, 702–4.Google Scholar
3 Braestrup, C. & Squires, R. F. (1977) Specific benzodiazepine receptors in rat brain characterized by high affinity 3H-diazepam binding. Proceedings of the National Academy of Sciences, U.S.A., 74, 3805–9.CrossRefGoogle ScholarPubMed
4 Chang, R. S. L. & Snyder, S. H. (1978) Benzodiazepine receptors: Labeling in intact animals with 3H-Flunitrazepam. European Journal of Pharmacology, 48, 213–18.CrossRefGoogle Scholar
5 Choi, D. W., Farb, D. H. & Fischbach, G. D. (1977) Chlordiazepoxide selectively augments GABA action in spinal cord cell culture. Mature, 260, 342–4.Google Scholar
6 Enna, S. J. & Snyder, S. H. (1975) Properties of γ-Aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions. Brain Research, 100, 81–97.CrossRefGoogle ScholarPubMed
7 Haefely, W., Kulcsar, A., Möhler, H., Pieri, L., Polc, P. & Schaffner, R. (1975) Possible involvement of GABA in the central actions of benzodiazepines. Advances in Biochemical Pharmacology, 14, 131–51.Google Scholar
8 Haefely, W. E. (1978) Behavioural and neuropharmacological aspects of drugs used in anxiety and related states. In Psychopharmacology: A Generation of Progress (ed Lipton, M. A., DiMascio, A., Killam, K. F.). New York: Raven Press, pp 1359–74.Google Scholar
9 Möhler, H., Okada, T., Ulrich, J. & Heitz, Ph. (1978) Biochemical identification of the site of action of benzodiazepines in human brain by 2H-diazepam binding. Life Sciences, 22, 985–96.CrossRefGoogle ScholarPubMed
10 Möhler, H. & Okada, T. (1977) Benzodiazepine receptor: Demonstration in the central nervous system. Science, 198, 849–51.Google Scholar
11 Möhler, H. & Okada, T. (1977) Properties of 3H-diazepam binding to benzodiazepine receptors in rat cerebral cortex. Life Sciences, 20, 2101–10.CrossRefGoogle ScholarPubMed
12 Möhler, H. & Okada, T. (1977) GABA receptor binding with 3H (+) bicuculline-methiodide in rat CNS. Nature, 267, 65–7.Google Scholar
13 Müller, W. E. & Wollert, U. (1976) Benzodiazepines: Specific competitors for the binding of L-tryptophan to human serum albumin. Naunyn Schmiedeberg's Archives of Pharmacology, 288, 17–27.Google Scholar
14 Okada, T. & Möhler, H. Ligand specificity of the brain benzodiazepine receptor. In preparation.Google Scholar
15 Okada, T. Spokes, E. G., Bird, E. D. & Möhler, H. (1978) Huntington's chorea: decrease in benzodiazepine receptor binding in putamen and caudate nucleus. In preparation.Google Scholar
16 Polc, P., Möhler, H. & Haefely, W. E. (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
17 Ringel, S. P., Guthrie, M. & Klawans, H. L. (1973) Current treatment of Huntington's chorea. In Advances in Neurology (ed Barbeau, A., Chase, T. and Paulson, G. W.). New York: Raven Press, Vol. 1, 797–801.Google Scholar
18 Snyder, S. H. & Bennett, J. P. (1976) Neurotransmitter receptors in the brain: biochemical identification. Annual Review of Physiology, 38, 153–75.Google Scholar
19 Squires, R. F. & Braestrup, C. (1977) Benzodiazepine receptors in rat brain. Nature, 266, 732–4.CrossRefGoogle ScholarPubMed
20 Zukin, S. R., Young, A. B. & Snyder, S. H. (1974) Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system. Proceedings of the National Academy of Sciences U.S.A., 71, 4802–7.Google Scholar
21 Bird, E. D. & Iversen, L. L. (1974) Huntington's chorea: post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia. Brain, 97, 457–72.CrossRefGoogle ScholarPubMed
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