Original Investigations


, Volume 83, Issue 3, pp 249-256

Evaluation of the β-carboline ZK 93 426 as a benzodiazepine receptor antagonist

  • Leif H. JensenAffiliated withA/S Ferrosan, Research Division
  • , Erling N. PetersenAffiliated withA/S Ferrosan, Research Division
  • , Claus BraestrupAffiliated withA/S Ferrosan, Research DivisionSt Hans Mental Hospital
  • , Tage HonoréAffiliated withA/S Ferrosan, Research Division
  • , Wolfgang KehrAffiliated withSchering AG
  • , David N. StephensAffiliated withSchering AG
  • , Herbert SchneiderAffiliated withSchering AG
  • , Dieter SeidelmannAffiliated withSchering AG
  • , Ralph SchmiechenAffiliated withSchering AG

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We describe here biochemical and pharmacological effects of the β-carboline ZK 93426, a new and potent benzodiazepine (BZ) receptor antagonist. ZK 93426 was compared with Ro 15-1788 and CGS 8216, two compounds previously described as BZ receptor antagonists. Certain effects of ZK 93426, Ro 15-1788 and CGS 8216 were quite similar (e.g., 3H-FNM displacement, “GABA ratio”, “photo-shift”). In most pharmacological tests ZK 93426 and Ro 15-1788 lacked overt effects; Ro 15-1788 was a weak agonist in some paradigms, while ZK 93426 exhibited a potent proconflict effect but also a weak anticonvulsant effect. This interesting finding with ZK 93426 suggests that BZ receptor ligands may possess differential efficacy at BZ receptor subtypes. In contrast, CGS 8216 exhibited potent proconvulsant effects in several paradigms in addition to proconflict and pentylenetetrazol generalizing effects. ZK 93426, Ro 15-1788 and CGS 8216 were almost equally potent as antagonists of the effects of BZ receptor agonists, such as diazepam and lorazepam. However, ZK 93426 was the most potent inhibitor of the convulsions produced by the BZ receptor inverse agonist DMCM.

Key words

ZK 93426 Ro 15-1788 CGS 8216 Benzodiazepine receptor agonists Benzodiazepine receptor antagonist Benzodiazepine receptor inverse agonist Rat Mouse