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  • 1
    Electronic Resource
    Electronic Resource
    The sedative effects of CL 218,872, like those of chlordiazepoxide, are reversed by benzodiazepine antagonists (1985)
    Springer
    Psychopharmacology 85 (1985), S. 295-300 
    Details
    ISSN: 1432-2072
    Keywords: Exploration ; Locomotor activity ; Sedation ; Chlordiazepoxide ; Benzodiazepine ; CL 218,872 ; Benzodiazepine antagonists ; Ro 15-1788 ; CGS 8216 ; Rat ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of CL 218,872, initially classified as a non-sedative anxiolytic, were investigated and compared with those of chlordiazepoxide in the holeboard. The ability of two drugs that antagonise the effects of benzodiazepines, CGS 8216 and Ro 15-1788, to reverse the effects of CL 218,872 and chlordiazepoxide were also investigated, to see whether their effects might be mediated via benzodiazepine receptors. CL 218,872 (10 mg/kg) was found to be significantly sedative in both mice and rats (i.e., both locomotor activity and head-dipping were significantly decreased). In mice, the effects of CL 218,872 and of chlordiazepoxide were very similar over a range of doses, except that the stimulatory effect seen with low doses of chlordiazepoxide on head-dipping just failed to reach significance with CL 218,872. This study is in agreement with recently published results from different tests showing that sedative effects can be obtained with doses of CL 218,872 that are low and not much higher than those leading to anxiolysis. The sedative effects of both CL 218,872 (10 mg/kg) and chlordiazepoxide (20 mg/kg) were significantly reversed by RO 15-1788 (10 and 20 mg/kg) and CGS 8216 (10 mg/kg), suggesting that their effects are mediated via benzodiazepine receptors. The increase in head-dipping seen with chlordiazepoxide (2.5 mg/kg) was also reversed by RO 15-1788 and CGS 8216.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428190
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  • 2
    Electronic Resource
    Electronic Resource
    The role of the benzodiazepine receptor in mediating long-lasting anticonvulsant effects and the late-appearing reductions in motor activity and exploration (1989)
    Springer
    Psychopharmacology 97 (1989), S. 349-354 
    Details
    ISSN: 1432-2072
    Keywords: Benzodiazepine ; Sedation ; Exploration ; Mouse ; Anticonvulsant ; Receptor occupancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The number of head-dips, the time spent head-dipping, the number of rears and the locomotor activity of mice placed in a holeboard was reduced by lorazepam (0.25 mg/kg) 1 and 1.5 h after oral administration and these reductions were reversed by the benzodiazepine antagonist flumazenil (1 mg/kg). Activity returned to control levels at 3 and 4.5 h for head-dipping, and between 3 and 12 h for rearing and locomotor activity. However, significant late-appearing reductions were found for the number of head-dips and the time spent head-dipping (6 h) and rearing and locomotor activity (15 h) and these decreases could not be reversed by flumazenil. Similar results were found after oral administration of oxazepam (7 mg/kg). Oxazepam reduced the number of head-dips and time spent head-dipping at 1, 1.5 and 3 h and these reductions were reversed by flumazenil (1 mg/kg). Head-dipping activity returned to normal at 4.5 h. Significant reductions were also found for both measures at 1, 6 and 7.5 h and these late reductions could not be reversed by flumazenil. This suggests that the late-appearing reductions in holeboard behaviours, resulting from lorazepam or oxazepam administration to mice, is not mediated by the benzodiazepine receptor. This conclusion was supported by the results from in vivo binding, which showed no change in the % receptor occupancy 3–15 h after administration of lorazepam or oxazepam. In contrast to the holeboard behaviours, the anticonvulsant effects of the two drugs showed good correlations with receptor occupancy. The anticonvulsant effect of oxazepam (7 mg/kg) significantly decreased 1–3 h after oral administration, but thereafter a steady anticonvulsant effect was retained for up to 24 h. The anticonvulsant effect of lorazepam (0.25 mg/kg) also significantly decreased 1–3 h after administration, and thereafter remained steady for up to 15 h. At all the time-points tested, oxazepam (7 mg/kg) had a significantly greater anticonvulsant effect than lorazepam (0.25 mg/kg). This was mirrored by higher percentage receptor occupancies in cortex, hippocampus and cerebellum, from 3 to 15 h after administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00439449
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Changes in seizure threshold and aggression during chronic treatment with three anticonvulsants and on drug withdrawal (1990)
    Springer
    Psychopharmacology 100 (1990), S. 237-242 
    Details
    ISSN: 1432-2072
    Keywords: Barbiturate ; Diphenylhydantoin ; Benzodiazepine ; Anticonvulsant ; Aggression ; Social behaviour ; Tolerance ; Withdrawal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sodium phenobarbitone (20 and 70 mg/kg) had a significant anticonvulsant action against pentylenetetrazole-induced seizures, which persisted for 21 days of treatment. On drug withdrawal there was a significant decrease in seizure threshold below control level 24–48 h after the last dose of 70 mg/kg. Phenytoin (40 mg/kg) had a significant anticonvulsant action after 7 days of treatment and this persisted for 21 days of treatment. On drug withdrawal there was a significant decrease in seizure threshold 48 h after the last dose. Lorazepam (0.1 mg/kg) had a significant anticonvulsant action, but the group tested after 21 days of treatment did not differ from the controls, indicating that tolerance had developed to this effect; on drug withdrawal there was a decrease in seizure threshold from 24 to 72 h. The only drug to increase aggressive behaviour was sodium phenobarbitone (70 mg/kg); this reached significance after 14 and 21 days of treatment and occurred 8 h after drug administration; 0.5 h after drug administration phenobarbitone (70 mg/kg) abolished aggressive behaviour. After 7 days of treatment phenobarbitone (70 mg/kg) increased social behaviour 0.5 h after administration and this was still increased after 21 days of treatment. On drug withdrawal, there were no changes in aggressive behaviour, but there were significant decreases in social behaviour 24 and 48 h after phenobarbitone (70 mg/kg) withdrawal and 24, 48 and 72 h after lorazepam (0.1 mg/kg) withdrawal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244413
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    Paper (German National Licenses)
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