Abstract
3H-Ro 15-1788, a benzodiazepine receptor antagonist, was injected IV into male and pregnant mice. Autoradiograms were prepared from sagittal sections of animals killed after 30 s to 48 h. In the adult animal there was a rapid and high initial accumulation of radioactivity in the brain as compared to other organs and tissues. The highest accumulation was found in cortical brain areas, such as the olfactory bulb and the frontal cortex. Cerebellar cortex, globus pallidus, amygdala, substantia nigra, colliculus, hippocampus and pons followed in rank order. The rate of decline of radioactivity was highest in the pons and lowest in the olfactory bulb. The initial disappearance of radioactivity from the cerebellum was higher than from the other brain regions. Ro 15-1788 was rapidly eliminated; 4 h after drug administration there was an almost complete clearance of radioactivity from all tissues. After 24 h no trace of activity remained in the animal. The distribution of radioactivity at later time points indicates that metabolites of Ro 15-1788 are eliminated by fecal, urinary and nasal secretion. In the fetus also there was an early accumulation of radioactivity in the central nervous system. The radioactivity in fetal organs was lower than in the mother at all time intervals.
Similar content being viewed by others
References
Braestrup C, Nielsen ML (1981) 3H-Propyl-β-carbolin-3-carboxylate as a selective radioligand for the BZ 1 — benzodiazepine receptor subclass. J Neurochem 37:333–341
Goeders N, Kuhar MJ (1985) Benzodiazepine receptor binding in vivo with 3H-Ro 15–1788. Life Sci 37:345–355
Hantraye P, Kalhma M, Prenant C, Guibert B, Sastre J, Crouzei M, Naquet R, Comar D, Maziere M (1984) Central type benzodiazepine binding sites: A positron emission tomography study in the baboon's brain. Neurosci Lett 48:115–120
Hunkeler W, Möhler H, Pieri L, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516
Klotz U, Ziegler G, Reinman IW (1984) Pharmacokinetics of the selective benzodiazepine antagonist Ro 15–1788 in man. Eur J Clin Pharmacol 27:115–117
Lindquist N-G, Ullberg S (1972) The melanine affinity of chlorochine and chlorpromazine studied by whole-body autoradiography. Acta Pharmacol Toxicol [Suppl 2] 31:1–32
Lippa AS, Klepner CA, Benson DI, Crithcett DJ, Sano MC, Beer B (1980) The role of GABA in mediating the anticonvulsant properties of benzodiazepines. GABA neurotransmission. Brain Res Bull Suppl 2, 5:861–865
Maziere M, Prenant C, Sastre J, Grouse M, Comar D, Hantraye P, Kaijma M, Guibert B, Naquet R (1983) 11C-Ro 15–1788 et 11C-flunitrazepam, deux coordinants pour l-etude par tomographie par positrons des sites de liaison des benzodiazepines. C R Acad Sci, Paris 296, Serie 111:871–876
Möhler M, Burkard WP, Keller HH, Richards JG, Haefely W (1981) Benzodiazepine antagonist Ro 15–1788; binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cGMP levels. J Neurochem 37:714–722
Persson A, Ehrin E, Eriksson L, Farde L, Hedström C-G, Litton J-E, Mindus P, Sedvall G (1985) Imaging of 11C-labelled Ro 15–1788 to benzodiazepine receptors in the human brain by positron emission tomography. J Psychiatr Res 19; 4:609–622
Richards JG, Möhler H (1984) Benzodiazepine receptors. Neuropharmacology 23:233–242
Samson Y, Hantraye P, Baron JC, Soussaline F, Comar D, Maziere M (1985) Kinetics and displacement of 11C Ro 15–1788, a benzodiazepine antagonist, studied in human brain in vivo by positron tomography. Eur J Pharmacol 110:247–251
Ullberg S (1977) The technique of whole body autoradiography. Cryosectioning of large specimens. Sci Tools, The LKB Instrument Journal (Bromma, Sweden), Special issue on whole-body autoradiography, pp 1–29
Yamasaki T, Inoue O, Hashimoto K, Shiotoh H, Tateno Y, Ito T, Suzuki K, Kashida Y (1984) In vivo measurement of brain benzodiazepine receptor and its application. Academic, Japan
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
d'Argy, R., Persson, A. & Sedvall, G. A quantitative cerebral and whole body autoradiographic study of a intravenously administered benzodiazepine antagonist 3H-Ro 15-1788 in mice. Psychopharmacology 92, 8–13 (1987). https://doi.org/10.1007/BF00215472
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00215472