Biomarkers for the effects of benzodiazepines in healthy volunteers.

@article{deVisser2003BiomarkersFT,
  title={Biomarkers for the effects of benzodiazepines in healthy volunteers.},
  author={S J de Visser and J.P. van der Post and Paul P. de Waal and François Cornet and Adam F. Cohen and J. M. A. van Gerven},
  journal={British journal of clinical pharmacology},
  year={2003},
  volume={55 1},
  pages={
          39-50
        }
}
Studies of novel centrally acting drugs in healthy volunteers are traditionally concerned with kinetics and tolerability, but useful information may also be obtained from biomarkers of clinical endpoints. A useful biomarker should meet the following requirements: a consistent response across studies and drugs; a clear response of the biomarker to a therapeutic dose; a dose-response relationship; a plausible relationship between biomarker, pharmacology and pathogenesis. In the current review… 
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References

SHOWING 1-10 OF 73 REFERENCES
Biomarkers for the effects of antipsychotic drugs in healthy volunteers.
TLDR
Subjective and objective measures of alertness, and of visual-visuomotor-auditory and motor skills were most sensitive to antipsychotics, although over half of all the studies failed to show statistically significant differences from placebo.
Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.
TLDR
The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.
A study of the effects of long-term use on individual sensitivity to temazepam and lorazepam in a clinical population.
TLDR
Chronic users of lorazepam show evidence of tolerance to sedative effects in comparison with healthy controls and the difference may be related to pharmacological properties, in addition to different patterns of use, associated with psychological factors.
Differences in pharmacodynamics but not pharmacokinetics between subjects with panic disorder and healthy subjects after treatment with a single dose of alprazolam.
TLDR
After alprazolam treatment, there was increased sensitivity to EEG and mood effects and fewer aversive effects in the panic disorder group compared with healthy subjects and there were no differences in the pharmacodynamic measures of sedation and cognition or differences in pharmacokinetics between the two groups.
Prediction of the therapeutic dose for benzodiazepine anxiolytics based on receptor occupancy theory.
TLDR
A possible system for estimating the appropriate doses of BZPs based on receptor occupancy theory is developed and the mechanism of the differences in therapeutic dose by retrospective analyses is clarified and a system for the quantitative estimation of optimal doses is developed.
Intravenous alprazolam challenge in normal subjects
TLDR
Alprazolam's effects on growth hormone resemble those of clonidine, but unlike clonalid, alprazoam has relatively little effect on plasma catecholamine and cardiovascular parameters, which suggests that α2 mechanisms do not play a primary role in alpazolam’s mode of action.
Vigilance impairment after a single dose of benzodiazepines
TLDR
Only diazepam 5mg and 10 mg, alprazolam 0.5 mg, and nitrazepam 5 mg caused significant deterioration in vigilance performance along with perceived sleepiness and the need for a greater effort to overcome it.
Effects of single doses of alpidem, lorazepam, and placebo on memory and attention in healthy young and elderly volunteers.
TLDR
Alpidem, a new imidazopyridine derivative with benzodiazepine-like anxiolytic effects, with those of lorazepam and placebo on memory and attention in two age groups of healthy volunteers produced memory impairments and no significant drug effects on attention.
[Benzodiazepine antagonism by RO 15-1788: psychometric, hormonal and biophysical parameters].
TLDR
Whether a high dose of Ro 15-1788 can precipitate withdrawal reactions relating to behavior and changes in the stress-hormone plasma levels after acute BZD treatment in man is examined.
Age-related increase in CNS sensitivity to benzodiazepines as assessed by task difficulty
TLDR
Evidence of increased drug sensitivity in the elderly was provided by the more prolonged duration of the pharmacologic effect in the older than young subjects, especially for the harder versions of the SCT and DSS tasks.
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