Topic
Divaplon
About: Divaplon is a research topic. Over the lifetime, 3 publications have been published within this topic receiving 71 citations.
Papers
TL;DR: Results show that BZ (ω) receptor partial agonists without apparent sedative actions can disrupt fear learning, indicating that the effects of this class of drugs on passive avoidance learning can be dissociated from sedation.
Abstract: It is well established that benzodiazepines can produce anterograde amnesia in humans and interfere with the acquisition of passive avoidance and spatial responses in rodents However, the extent to which the disruption of learning is a secondary effect of the sedation produced by these drugs has not been clearly established In order to investigate this question, the effects of several BZ (ω) receptor partial agonists were studied on the acquisition of conditioned fear (passive avoidance learning) in mice As these drugs have been shown to produce anticonvulsant and anxiolytic-like effects without sedation or depression of motor activity, it was of interest to see whether they could disrupt learning Clear effects on the acquisition of conditioned fear were produced by imidazenil (001–10 mg/kg), divaplon (1–60 mg/kg), ZK 91296 (3–60 mg/kg), and Ro 17-1812 (01–10 mg/kg) However, bretazenil (01–10 mg/kg) did not produce statistically significant effects Only the high dose of imidazenil (10 mg/kg) decreased levels of exploratory behaviour These results show that BZ (ω) receptor partial agonists without apparent sedative actions can disrupt fear learning, indicating that the effects of this class of drugs on passive avoidance learning can be dissociated from sedation The reasons for the observed differences between the different compounds studied are unclear at present and may be related to differences in intrinsic activity or receptor subtype selectivity
7 citations
Journal Article•
TL;DR: The partial agonism postulated for bretazenil and divaplon on pharmacological grounds is shown to be operative on the level of single GABAA receptors, demonstrating that the intrinsic activity of benzodiazepine receptor ligands can vary among the receptor subtypes with the degree of receptor modulation being influenced by the type of alpha subunit.
Abstract: The differences in intrinsic activity and receptor subtype specificity of the newly developed benzodiazepine receptor ligands bretazenil, divaplon and abecarnil were assessed in recombinant gamma-aminobutyric acidA (GABAA) receptors expressed in mammalian cells from the subunit-cDNA combinations alpha 3 beta 2 gamma 2 and alpha 5 beta 2 gamma 2. Chloride currents induced by rapid application of GABA in the presence or absence of drugs were measured using the whole-cell configuration of the patch-clamp technique. Bretazenil displayed an intrinsic activity which amounted only to 58 +/- 7% and 35 +/- 11% of that of flunitrazepam at the alpha 3 beta 2 gamma 2 and alpha 5 beta 2 gamma 2 combination, respectively. The maximum potentiation by divaplon was only 28 +/- 5% and 21 +/- 9% of that of flunitrazepam at the respective subunit combinations. Thus, the partial agonism postulated for bretazenil and divaplon on pharmacological grounds is shown to be operative on the level of single GABAA receptors. Most strikingly, abecarnil potentiated the GABA response to the same degree as flunitrazepam at the alpha 3 beta 2 gamma 2 combination but to only 52 +/- 14% compared to flunitrazepam at the alpha 5 beta 2 gamma 2 combination. This finding demonstrates that the intrinsic activity of benzodiazepine receptor ligands can vary among the receptor subtypes with the degree of receptor modulation being influenced by the type of alpha subunit.
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 1995 | 1 |
| 1993 | 2 |