used in combat to protect troops in the event of exposure to chemical warfare agents. These studies were reviewed for reports of general health outcomes and adverse effects on different organ systems.

Neuromuscular Studies in Healthy Volunteers

In a double-blind, placebo-controlled crossover study, Graham and Cook (1984) evaluated the effects of PB on 24 healthy male volunteers between the ages of 21 and 35, measuring a wide variety of performance measures including neuromuscular strength by grip testing and perceived level of exertion. Thirty milligrams of oral PB or placebo was administered three times daily for 5 days. No significant difference in strength or perceived exertion between PB and placebo-treated subjects was observed. The PB regimen produced the expected mean level of inhibition of plasma ChE, although large variation in inhibition between individuals was observed. No evidence of adverse health effects was found.

In another double-blind, placebo-controlled study of 35 healthy volunteers, Glikson and colleagues (1991) measured the effects of oral dosing of PB on direct tests of muscle strength and endurance. Subjects received either PB as 30-mg tablets or a placebo every 8 hours for 10 days. Before and during treatment, four subjects in the PB group and two in the placebo group also underwent electrodiagnostic studies (e.g., electromyography [EMG], nerve conduction velocity, and repetitive strength testing) of neuromuscular function. Subjects (16 placebo and 19 PB treated) underwent baseline tests of these parameters and were retested after 8 days of treatment and again 5 days after the cessation of treatment. Blood AChE levels showed a mean decrement of 23 percent, compared to baseline, among PB-treated subjects during therapy. Posttherapy AChE levels were identical to baseline.

Test parameters were analyzed as the percentage change from baseline for every variable in each subject. Measurements of handgrip strength as well as isokinetic elbow flexor and extensor strength did not differ between the placebo and PB groups. Electrodiagnostic studies of subjects treated with PB showed no significant change from baseline during or after the treatment. Some direct, standardized measurements of muscle strength (knee flexor and isokinetic strength) showed a small but statistically significant improvement on day 8 among placebo- but not PB-treated subjects. Conversely, knee extensor endurance showed a slight but statistically significant decrease on day 8 in the placebo group, whereas this variable remained unchanged in PB-treated subjects. Posttreatment strength measurements were not significantly different from baseline in either group.

The authors attributed the differences in some measures of muscle strength and endurance to large fluctuations in performance among the placebo group. It is possible that the improvement in knee flexor and extensor muscle strength at day 8 among placebo-treated subjects reflected only a training effect that was prevented by PB in the treatment group. However this would not explain the return to baseline 5 days posttreatment. The slight but statistically significant



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement