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Do alprazolam-induced changes in saccadic eye movement and psychomotor function follow the same time course?
P D Kroboth1, M M Folan, K S Bauer
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pennsylvania 15261, USA.
Journal of Clinical Pharmacology
|May 20, 1998
Summary
Short-term tolerance develops to GABA-agonist effects on saccadic eye movements (SEMs) and psychomotor function. SEMs are more sensitive than psychomotor tests to GABA-agonist drug effects, indicating tolerance development.
Area of Science:
- Neuroscience
- Pharmacology
- Ophthalmology
Background:
- GABA-agonist drugs, like alprazolam, affect central nervous system functions.
- Saccadic eye movements (SEMs) and psychomotor function are sensitive to drug-induced impairment.
Purpose of the Study:
- To investigate short-term tolerance to GABA-agonist-induced changes in SEMs.
- To compare the time course of impairment and recovery for SEMs and psychomotor function.
- To assess the relative sensitivity of SEMs and psychomotor function to GABA-agonist effects.
Main Methods:
- A balanced, double-blind, three-way crossover study involving six healthy volunteers.
- Administration of placebo, a compressed tablet (CT) of alprazolam, and a sustained-release (SR) tablet of alprazolam.
- Assessment of SEMs and psychomotor function at regular intervals after drug administration.
Main Results:
- Both SEMs and psychomotor tests showed tolerance development over time.
- SEMs detected differences in drug absorption rates between CT and SR formulations.
- SEMs exhibited impairment that persisted longer than psychomotor impairment.
Conclusions:
- Short-term tolerance develops to GABA-agonist effects on both SEMs and psychomotor function.
- SEMs are a more sensitive indicator of GABA-benzodiazepine receptor complex activity than psychomotor responses.
- The high GABA dependency and low motivation sensitivity of SEMs contribute to their heightened sensitivity.