Individual Differences in Neurobehavioral Effects of Pyridostigmine
Final rept. 30 Sep 1997-31 Jan 2001
MIDWEST RESEARCH INST KANSAS CITY MO
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We conducted two double-blind studies designed to test the following specific hypotheses about pyridostigmine bromide PB a under well-controlled conditions, AChE andor BuChE inhibition will be related to alterations in the performance of complex tasks, heart rate variability HRV, and peripherally mediated measures of physiological and sensorimotor functions b individual differences can be differentiated from pharmacokinetic variability by use of a dose-response design, and c PB will produce more centrally-mediated effects under heat stress. Both studies were double-blind, placebo-controlled, crossover design. Volunteers were 18-35 yrs of age. In Study 1, physiological, sensorimotor, and cognitive measures were collected. In addition, plasma and urinary PB and 3-hydroxy-N-methylpyridinium bromide THMP, the major metabolite of PB, as well as AChE and BuChE, were measured. These endpoints were measured, time- locked to time of intake of the pills and time of the test battery. Significant PB effects on heart rate and heart rate variability were observed. In study 2, volunteers were exposed to heat prior to and during testing on the other day, they were tested at normal room temperature. Study 1 findings on side effects, heart rate and heart rate variability were replicated.
- Medicine and Medical Research
- Stress Physiology