Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Jan;105(1):8–10. doi: 10.1111/j.1476-5381.1992.tb14201.x

The antagonism of benzodiazepine withdrawal effects by the selective cholecystokininB receptor antagonist CI-988.

L Singh 1, M J Field 1, C A Vass 1, J Hughes 1, G N Woodruff 1
PMCID: PMC1908629  PMID: 1350747

Abstract

The ability of a selective cholecystokininB (CCKB) receptor antagonist, CI-988, to block benzodiazepine withdrawal effects was examined in mice. The discontinuation of twice daily administration of diazepam (1 mg kg-1, i.p.) induced withdrawal anxiogenesis and a proconvulsant effect. In contrast, no such effects were seen following withdrawal from similar administration of CI-988. However, CI-988 dose-dependently (0.001-1.0 mg kg-1, s.c.) antagonized both the anxiogenesis and the proconvulsant effect following diazepam-withdrawal.

Full text

PDF
8

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bouthillier A., De Montigny C. Long-term benzodiazepine treatment reduces neuronal responsiveness to cholecystokinin: an electrophysiological study in the rat. Eur J Pharmacol. 1988 Jun 22;151(1):135–138. doi: 10.1016/0014-2999(88)90703-0. [DOI] [PubMed] [Google Scholar]
  2. Emmett-Oglesby M. W., Mathis D. A., Moon R. T., Lal H. Animal models of drug withdrawal symptoms. Psychopharmacology (Berl) 1990;101(3):292–309. doi: 10.1007/BF02244046. [DOI] [PubMed] [Google Scholar]
  3. Goa K. L., Ward A. Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. Drugs. 1986 Aug;32(2):114–129. doi: 10.2165/00003495-198632020-00002. [DOI] [PubMed] [Google Scholar]
  4. Harro J., Lang A., Vasar E. Long-term diazepam treatment produces changes in cholecystokinin receptor binding in rat brain. Eur J Pharmacol. 1990 May 3;180(1):77–83. doi: 10.1016/0014-2999(90)90594-v. [DOI] [PubMed] [Google Scholar]
  5. Hughes J., Boden P., Costall B., Domeney A., Kelly E., Horwell D. C., Hunter J. C., Pinnock R. D., Woodruff G. N. Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6728–6732. doi: 10.1073/pnas.87.17.6728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Moreau J. L., Jenck F., Pieri L., Schoch P., Martin J. R., Haefely W. E. Physical dependence induced in DBA/2J mice by benzodiazepine receptor full agonists, but not by the partial agonist Ro 16-6028. Eur J Pharmacol. 1990 Nov 6;190(1-2):269–273. doi: 10.1016/0014-2999(90)94138-n. [DOI] [PubMed] [Google Scholar]
  7. Schweizer E., Rickels K., Lucki I. Resistance to the anti-anxiety effect of buspirone in patients with a history of benzodiazepine use. N Engl J Med. 1986 Mar 13;314(11):719–720. doi: 10.1056/NEJM198603133141121. [DOI] [PubMed] [Google Scholar]
  8. Singh L., Field M. J., Hughes J., Menzies R., Oles R. J., Vass C. A., Woodruff G. N. The behavioural properties of CI-988, a selective cholecystokininB receptor antagonist. Br J Pharmacol. 1991 Sep;104(1):239–245. doi: 10.1111/j.1476-5381.1991.tb12413.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Singh L., Lewis A. S., Field M. J., Hughes J., Woodruff G. N. Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1130–1133. doi: 10.1073/pnas.88.4.1130. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES