ZK 93426 hydrochloride

Enhancement of gamma-aminobutyric acid binding by the anxiolytic beta-carbolines ZK 93423 and ZK 91296.[Pubmed:2881979]

J Neurochem. 1987 May;48(5):1355-8.

The effects of two anxiolytic beta-carboline derivatives, ZK 93423 and ZK 91296, on the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to brain membrane preparations from rat cerebral cortex were examined. ZK 93423 concentration-dependently enhanced the specific binding of [3H]GABA, with a maximal increase of 45% above control at a 50 microM concentration. A less pronounced increase was induced by diazepam and by the partial agonist ZK 91296. Scatchard plot analysis revealed that the effect of ZK 93423 was due to an increase in the total number of high- and low-affinity GABA binding sites. The action of ZK 93423 was mediated by benzodiazepine recognition sites since it was blocked by the benzodiazepine antagonists Ro 15-1788 and ZK 93426 at concentrations that failed to modify [3H]GABA binding on their own. Moreover the stimulatory effect of ZK 93423 on [3H]GABA binding was also blocked by the beta-carboline inverse agonist ethyl beta-carboline-3-carboxylate. These results are consistent with the view that ZK 93423 and ZK 91296, similarly to benzodiazepines, exert their pharmacological effects by enhancing the GABAergic transmission at the level of the GABA/benzodiazepine receptor complex.

Effects of beta-carbolines in animal models of anxiety.[Pubmed:3315125]

Brain Res Bull. 1987 Sep;19(3):293-9.

Animal models of anxiety can be classified into three main groups: those based on conflict or conditioned fear; those exploiting the anxiety produced by novelty; those in which anxiety or aversion is chemically induced. This review briefly describes the existing tests and, where available, the results obtained with beta-carbolines. Many of the beta-carbolines are anxiogenic in the tests, however ZK 91296 and ZK 93423 appear to have anxiolytic properties, and ZK 93426 has a similar profile to that of the benzodiazepine receptor antagonist RO 15-1788. By the results across the spectrum of tests, the reliability and sensitivity of the tests is assessed. The evidence that the anxiogenic and anxiolytic actions of the beta-carbolines are mediated by the BDZ binding sites is also discussed.

Evaluation of the beta-carboline ZK 93 426 as a benzodiazepine receptor antagonist.[Pubmed:6089247]

Psychopharmacology (Berl). 1984;83(3):249-56.

We describe here biochemical and pharmacological effects of the beta-carboline 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.