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. 1985 Nov;86(3):729–735. doi: 10.1111/j.1476-5381.1985.tb08952.x

The effects of triazolobenzodiazepines in two animal tests of anxiety and in the holeboard.

S E File, S Pellow
PMCID: PMC1916742  PMID: 2866006

Abstract

In addition to possessing anti-anxiety activity in man, triazolobenzodiazepines have been reported to have antidepressant and antipanic properties. In this they differ from classical 1,4-benzodiazepines that have only anti-anxiety activity. The purpose of the present study was to examine the effects of the triazolobenzodiazepines in two animal tests of anxiety and in the holeboard, to see whether clear differences could be observed between them and the 1,4-benzodiazepines. After acute administration, U-43,465 (16 mg kg-1) had a significant anxiolytic effect in the social interaction test. Neither adinazolam (1-3.5 mg kg-1) nor alprazolam (0.125-2 mg kg-1) had a significant effect. It is suggested that this is because, with adinazolam and alprazolam, doses at which anxiolytic effects can be observed are close to those at which sedative effects can be observed. U-43,465 (8-16 mg kg-1) and alprazolam (1-2 mg kg-1) had significant anxiolytic effects in the elevated plus-maze test of anxiety. U-43,465 (8-32 mg kg-1), adinazolam (0.5-5 mg kg-1) and alprazolam (0.2-2.0 mg kg-1) caused dose-related reductions in exploratory head-dipping, locomotor activity and rearing in the holeboard. In general the results seen in the three tests with the triazolobenzodiazepines alprazolam and adinazolam were similar to those seen with classical 1,4-benzodiazepines. With U-43,465, however, an anxiolytic effect was observed in the social interaction test after acute treatment; chronic treatment is required to see an effect with classical 1,4-benzodiazepines. In this U-43,465 resembles the effects of several novel non-benzodiazepine putative anxiolytic compounds that are believed to have less sedative potential than the benzodiazepines.

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Selected References

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  1. Ansseau M., Ansoms C., Beckers G., Bogaerts M., Botte L., De Buck R., Diricq S., Dumortier A., Jansegers E., Owieczka J. Double-blind clinical study comparing alprazolam and doxepin in primary unipolar depression. J Affect Disord. 1984 Dec;7(3-4):287–296. doi: 10.1016/0165-0327(84)90050-8. [DOI] [PubMed] [Google Scholar]
  2. Boulenger J. P., Uhde T. W. Le traitement des attaques de panique. Encephale. 1983;9(4 Suppl 2):299B–305B. [PubMed] [Google Scholar]
  3. Chouinard G., Annable L., Fontaine R., Solyom L. Alprazolam in the treatment of generalized anxiety and panic disorders: a double-blind placebo-controlled study. Psychopharmacology (Berl) 1982;77(3):229–233. doi: 10.1007/BF00464571. [DOI] [PubMed] [Google Scholar]
  4. Cohn J. B. Multicenter double-blind efficacy and safety study comparing alprazolam, diazepam and placebo in clinically anxious patients. J Clin Psychiatry. 1981 Sep;42(9):347–351. [PubMed] [Google Scholar]
  5. Davison K., Farquharson R. G., Khan M. C., Majid A. A double-blind comparison of alprazolam, diazepam and placebo in the treatment of anxious out-patients. Br J Clin Pharmacol. 1985;19 (Suppl 1):37S–43S. doi: 10.1111/j.1365-2125.1985.tb02741.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. File S. E. Animal models for predicting clinical efficacy of anxiolytic drugs: social behaviour. Neuropsychobiology. 1985;13(1-2):55–62. doi: 10.1159/000118163. [DOI] [PubMed] [Google Scholar]
  7. File S. E., Hyde J. R. A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants. Pharmacol Biochem Behav. 1979 Jul;11(1):65–69. doi: 10.1016/0091-3057(79)90298-3. [DOI] [PubMed] [Google Scholar]
  8. File S. E. The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods. 1980 Jun;2(3):219–238. doi: 10.1016/0165-0270(80)90012-6. [DOI] [PubMed] [Google Scholar]
  9. File S. E., Wardill A. G. Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacologia. 1975 Oct 14;44(1):53–59. doi: 10.1007/BF00421184. [DOI] [PubMed] [Google Scholar]
  10. File S. E. What can be learned from the effects of benzodiazepines on exploratory behavior? Neurosci Biobehav Rev. 1985 Spring;9(1):45–54. doi: 10.1016/0149-7634(85)90031-4. [DOI] [PubMed] [Google Scholar]
  11. Johnson D. A. The use of benzodiazepines in depression. Br J Clin Pharmacol. 1985;19 (Suppl 1):31S–35S. doi: 10.1111/j.1365-2125.1985.tb02740.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lahti R. A., Sethy V. H., Barsuhn C., Hester J. B. Pharmacological profile of the antidepressant adinazolam, a triazolobenzodiazepine. Neuropharmacology. 1983 Nov;22(11):1277–1282. doi: 10.1016/0028-3908(83)90200-9. [DOI] [PubMed] [Google Scholar]
  13. O'Connor W. T., Earley B., Leonard B. E. Antidepressant properties of the triazolobenzodiazepines alprazolam and adinazolam: studies on the olfactory bulbectomized rat model of depression. Br J Clin Pharmacol. 1985;19 (Suppl 1):49S–56S. doi: 10.1111/j.1365-2125.1985.tb02742.x. [DOI] [PubMed] [Google Scholar]
  14. Sethy V. H., Hodges D. H., Jr Alprazolam in a biochemical model of depression. Biochem Pharmacol. 1982 Oct 1;31(19):3155–3157. doi: 10.1016/0006-2952(82)90103-4. [DOI] [PubMed] [Google Scholar]
  15. Thiebot M. H., Doare L., Puech A. J., Simon P. U 43,465F: a benzodiazepine with antidepressant activity? Interaction with Ro 15-1788 and d,1-propranolol. Eur J Pharmacol. 1982 Oct 15;84(1-2):103–106. doi: 10.1016/0014-2999(82)90163-7. [DOI] [PubMed] [Google Scholar]
  16. Von Voigtlander P. F., Puech A. J. U-43,465F: a triazolobenzodiazepine with pronounced antidepressant-like as well as anxiolytic activities in animals. Arch Int Pharmacodyn Ther. 1983 Nov;266(1):60–76. [PubMed] [Google Scholar]

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