CL 218872 antagonism of diazepam induced loss of righting reflex: Evidence for partial agonistic activity at the benzodiazepine receptor

Kelvin W. Gee, Roberta E. Brinton, Henry I. Yamamura

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

A recent hypothesis suggests that the "selective anxiolytic" activity of the triazolopyridazine, CL 218872, is a reflection of this compounds high affinity for a benzodiazepine (BZD) receptor subtype. Subsequent to this proposal, the observation was made that CL 218872 does not effectively discriminate BZD receptor subtypes in vvitro at physiological temperatures (37°C). Based upon this observation, a selective effect in vivo related to the high affinity of CL 218872 for a BZD receptor subtype appears unlikely. The present study provides evidence for an alternative hypothesis to explain the unique pharmacological properties of CL 218872. The ability of CL 218872 to antagonize diazepam induced loss of righting reflex and enhance the anticonvulsant effect of diazepam in mice suggests that this triazolopyridazine may act as a partial agonist at the BZD receptor. Compared to the pharmacologically active BZDs, the unique actions of CL 218872 may be related to the lower intrinsic activity of this compound.

Original languageEnglish (US)
Pages (from-to)1037-1040
Number of pages4
JournalLife Sciences
Volume32
Issue number9
DOIs
StatePublished - Feb 28 1983
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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