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PMID: 6292984 Published · ppublish English Journal Article

Benzodiazepine antagonist Ro 15-1788: neurological and behavioral effects.

Psychopharmacology ·Vol. 78 ·No. 1 ·1982-00-00 ·Pages 8-18

Bonetti EP, Pieri L, Cumin R, Schaffner R, Pieri M, Gamzu ER, Müller RK, Haefely W

Abstract

In neurological and behavioral studies in mice, rats, dogs and squirrel monkeys, the imidazobenzodiazepinone Ro 15-1788 acted as a potent benzodiazepine antagonist. The antagonistic activity was both preventive and curative and seen at doses at which no intrinsic effects were detected. It was highly selective in that it acted against CNS effects induced by benzodiazepines but not against those produced by other depressants, such as phenobarbitone, meprobamate, ethanol, and valproate. The onset of action was rapid even after oral administration. Depending on the animal species studied, the antagonistic effects lasted from a few hours to 1 day. The acute and subacute toxicity of Ro 15-1788 was found to be very low. Benzodiazepine-like effects were not seen.

MeSH Terms
Animals Avoidance Learning/drug effects Behavior, Animal/drug effects Benzodiazepinones/pharmacology Conditioning, Operant/drug effects Dogs Dose-Response Relationship, Drug Exploratory Behavior/drug effects Female Flumazenil Male Motor Activity/drug effects Motor Skills/drug effects Muridae Nervous System/drug effects Pentylenetetrazole/pharmacology Rabbits Rats Receptors, Drug/drug effects Receptors, GABA-A Reflex/drug effects Respiration/drug effects Saimiri Seizures/chemically induced
Chemicals
Benzodiazepinones Receptors, Drug Receptors, GABA-A Flumazenil Pentylenetetrazole
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Bonetti E P
Pieri L
Cumin R
Schaffner R
Pieri M
Gamzu E R
Müller R K
Haefely W
References (22)
22 references, click to expand
  1. Pharmacology of midazolam.
    Arzneimittelforschung. 1981;31(12a):2180-201 PMID: 6120698
  2. Diazepam receptor characterization: specific binding of a benzodiazepine to macromolecules in various areas of rat brain.
    FEBS Lett. 1977 Oct 15;82(2):368-72 PMID: 410665
  3. [Assays on application and antagonizing of benzodiazepines in cattle (author's transl)].
    Dtsch Tierarztl Wochenschr. 1982 Apr 6;89(4):137-42 PMID: 6124413
  4. Evidence for involvement of GABA in the action of benzodiazepines: studies on rat cerebellum.
    Adv Biochem Psychopharmacol. 1975;(14):113-30 PMID: 242198
  5. Continuous avoidance as a base-line for measuring behavioral effects of drugs.
    Psychopharmacologia. 1962 Oct 5;3:264-82 PMID: 13953494
  6. Investigation in man of the efficacy of a benzodiazepine antagonist, Ro 15-1788.
    Lancet. 1981 Jul 4;2(8236):8-10 PMID: 6113428
  7. Selective antagonists of benzodiazepines.
    Nature. 1981 Apr 9;290(5806):514-6 PMID: 6261143
  8. Behavioral effects of some psychopharmacological agents.
    Ann N Y Acad Sci. 1957 Mar 14;66(3):740-52 PMID: 13425256
  9. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding.
    Proc Natl Acad Sci U S A. 1977 Sep;74(9):3805-9 PMID: 20632
  10. GABA-benzodiazepine-barbiturate receptor interactions.
    J Neurochem. 1981 Jul;37(1):1-13 PMID: 6265597
  11. Naloxone blocks the effect of diazepam and meprobamate on conflict behaviour in rats.
    Pharmacol Biochem Behav. 1981 Jul;15(1):115-7 PMID: 7291219
  12. Agonist and antagonist benzodiazepine receptor interaction in vitro.
    Nature. 1981 Dec 24;294(5843):763-5 PMID: 6275273
  13. Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture.
    J Neurophysiol. 1981 Apr;45(4):621-31 PMID: 6262463
  14. Diazepam and (--)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons.
    Proc Natl Acad Sci U S A. 1981 Nov;78(11):7180-4 PMID: 6273918
  15. Electrophysiological studies on the specific benzodiazepine antagonist Ro 15-1788.
    Naunyn Schmiedebergs Arch Pharmacol. 1981 Jul;316(4):317-25 PMID: 7196507
  16. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse.
    Psychopharmacologia. 1968 Sep 20;13(3):222-57 PMID: 5679627
  17. Pharmacodynamic basis for the use of chlorpromazine in psychiatry.
    J Clin Exp Psychopathol. 1956 Jan-Mar;17(1):25-37 PMID: 13295380
  18. Use of the specific benzodiazepine antagonist, Ro 15-1788, in studies of physiological dependence on benzodiazepines.
    Experientia. 1982 Jul 15;38(7):833-4 PMID: 6809488
  19. Benzodiazepine receptor: demonstration in the central nervous system.
    Science. 1977 Nov 25;198(4319):849-51 PMID: 918669
  20. Molecular mechanisms mediating the action of diazepam on GABA receptors.
    Br J Psychiatry. 1978 Sep;133:239-48 PMID: 212152
  21. Benzodiazepine antagonist Ro 15-1788: binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cGMP levels.
    J Neurochem. 1981 Sep;37(3):714-22 PMID: 6268754
  22. Benzodiazepine antagonist Ro 15-1788 counteracts the prolactin-lowering effects of other benzodiazepines in rats.
    Neuroendocrinology. 1982;35(1):32-6 PMID: 6287328
Article Info
Journal
Psychopharmacology
Abbr.
Psychopharmacology (Berl)
ISSN
0033-3158
DOI
10.1007/BF00470579
Published
1982-00-00
Pages
8-18
Language
English
Region
Germany
NLM ID
7608025
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00470579 View journal details
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